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Dabrafenib affects BRAF
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Dabrafenib inhibits BRAF.
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Dabrafenib inhibits mutated BRAF. 10 / 10
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"On the other hand, vemurafenib and dabrafenib inhibit mutations of BRAF V600, which prevents oncogenic activities such as proliferation and evasion of immune response."

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"Dabrafenib is a potent inhibitor of mutant BRAF."

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"Tyrosine kinase inhibitors (TKI) such as gefitinib, osimertinib, and erlotinib target EGFR mutations found in lung cancers, lapatinib is a dual TKI that targets HER2 and neu and EGFR mutations and is applied to advanced or metastatic breast cancer, vemurafenib and dabrafenib target BRAF mutations in melanoma, and crizotinib, ceritinib, and alectinib target anaplastic lymphoma kinase fusions in lung cancers."

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"Both drugs target the mitogen activated protein kinase (MAPK) pathway : dabrafenib selectively inhibits mutant BRAF that constitutively activates the pathway, and trametinib selectively inhibits MEK1 and MEK2 proteins activated by RAF kinases."

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"Dabrafenib inhibits the mutant BRAF (BRAF mut) protein in melanomas with BRAF V600E and BRAF V600K genotypes."

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"Gene therapy Vemurafenib and dabrafenib are potent inhibitors of the kinase domain in mutant BRAF, approved for the treatment of metastatic melanoma with a V600E BRAF mutation."

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"BRAF inhibitors vemurafenib and dabrafenib, selectively block the mutant BRAF protein and prolong overall survival in patients with BRAF mutant melanoma [XREF_BIBR, XREF_BIBR]."

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"Dabrafenib inhibited BRAF mutant cell lines with a 284 times lower IC 50 than non mutant cell lines."

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"Dabrafenib (GSK2118436) is a selective inhibitor of mutant BRAF."

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"Although mutant BRAF (v-Raf murine sarcoma viral oncogene homolog B1) inhibitors such as vemurafenib and dabrafenib have achieved unprecedented clinical responses in the treatment of melanomas with activating mutations in BRAF, complete remission is rare and a proportion of mutant BRAF melanomas are less responsive to the inhibitors."
Dabrafenib inhibits BRAF-V600E. 10 / 10
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"Vemurafenib and dabrafenib selectively inhibit the BRAF V600E oncoprotein, thereby inhibiting this pathway that is important in melanoma tumorigenesis."

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"While treatment with selective BRAF (V600E) inhibitors (like vemurafenib or dabrafenib) leads to high response rates but short response duration, CTLA-4 blocking therapies induce sustained responses, but only in a limited number of patients."

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"If the BRAF V600E mutation is present, as determined by sequencing or mutation specific PCR based assays, patients are eligible to receive a BRAF V600E -selective inhibitor such as vemurafenib or dabrafenib."

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"Vemurafenib and other BRAF V600E inhibitors like dabrafenib (GlaxoSmithKline, currently in Phase III trials) inhibit the BRAF V600E monomer but are unable to block ligand mediated RAF-RAF dimers."

medscan
"The B-Raf(V600E) inhibitor dabrafenib selectively inhibits RIP3 and alleviates acetaminophen-induced liver injury. 46999999="V600E"}"

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"Although BRAF V600E -specific inhibitors such as vemurafenib and dabrafenib have only recently entered clinical practice for children whose tumors carry this mutation, initial reports are encouraging."

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"The reversible B-Raf inhibitor, dabrafenib (GSK2118436), which selectively inhibits B-Raf V600E mutant, was recently investigated in clinical trials [XREF_BIBR - XREF_BIBR]."

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"Dabrafenib is also an inhibitor of the V600E BRAF which, as mentioned above, plays a role in the regulation of cell growth [XREF_BIBR]."

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"BRAF V600E inhibitors including vemurafenib and dabrafenib show clinical responses in many cases of BRAF V600E mutated cancers."

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"Further, clinically approved B-Raf inhibitors, vemurafenib and dabrafenib inhibit the mutated B-Raf V600E enzyme, preventing MEK activation in patients with the mutation [74]."
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"In addition, dabrafenib is a well-known inhibitor of B-Raf, which suppresses the downstream Ras/Raf/ERK/MAPK pathway, which has been approved for clinical use for the treatment of non small cell lung cancer expressing B-Raf V600E mutations and in melanoma."

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"Vemurafenib and dabrafenib are small molecule inhibitors of BRAF approved for use in patients with advanced melanoma harbouring a V600 BRAF mutation (NCCN Practice Guidelines in Oncology melanoma version 4.2014 [www.nccn.org/professionals/physician_gls/pdf/melanoma.pdf])."

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"This has implications for combination treatment strategies in melanoma where BRAF and MEK kinase inhibitors such as dabrafenib and trametinib may make melanoma cells less permissive of TVEC viral replication and cellular lysis."

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"Combined BRAF and MEK inhibitors such as dabrafenib and trametinib, vemurafenib and cobimetinib, and encorafenib and binimetinib are US Food and Drug Administration (FDA)-approved to treat patients with BRAF V600 -mutated advanced melanoma."

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"Examples are imatinib, targeting a specific fusion protein of ABL kinase in chronic myeloid leukemia [XREF_BIBR], and vemurafenib and dabrafenib, targeting a mutant form of the protein kinase BRAF in metastatic melanoma [XREF_BIBR, XREF_BIBR]."

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"To report the diagnosis of acute VKH like syndrome as a complication from dabrafenib (a serine/threonine inhibitor of BRAF V600) and trametinib (a MEK inhibitor)."

medscan
"Selective BRAF inhibition by vemurafenib or dabrafenib has become approved standard treatment in BRAF V600 mutated advanced stage melanoma. 44999999="V600"}"

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"XREF_BIBR In addition, trials studying the combination of BRAF and MEK inhibitors such as dabrafenib and trametinib (an MEK1 and MEK2 inhibitor) indicated improved survival, and currently ongoing trials are studying the combination with checkpoint inhibitors."

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"BRAF V600 inhibitors such as vemurafenib and dabrafenib leading to the activation, of several mechanisms of resistance [XREF_BIBR]."

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"In patients with BRAFV600E positive melanoma enrolled in large randomized phase III studies, treatment with BRAF kinase inhibitors such as vemurafenib and dabrafenib resulted in response rates of over 50-60% and progression-free survival (PFS) of 6-7 months."
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Dabrafenib inhibits BRAF-V600K. 1 / 1
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"Dabrafenib inhibits the mutant BRAF (BRAF (mut)) protein in melanomas with BRAF (V600E) and BRAF (V600K) genotypes."
Dabrafenib activates BRAF.
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"Since both extracranial metastases and BM also exhibit a broad response to vemurafenib, dabrafenib and other drugs targeting oncogenic BRAF [XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR]."

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"Patients with ROS1 positive NSCLC are treated with crizotinib and those with BRAF V600 mutation positive advanced or metastatic NSCLC are treated with acombination of dabrafenib and trametinib."

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"There are three reports on pediatric patients with BRAF mutated brain tumors treated with dabrafenib."

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"Dabrafenib, which specifically targets and inhibits BRAF, similar to vemurafenib, may be associated with less cutaneous squamous cell carcinoma or keratoacanthoma than vemurafenib, although it is associated with more pyrexia."

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"Here, we report a complete response followed by clinical progression in a patient with a BRAF V600E-mutant brain tumor treated with dabrafenib."

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"Here we analyse 20 BRAF (V600)-mutant melanoma metastases derived from 10 patients treated with the combination of dabrafenib and trametinib for resistance mechanisms and genetic correlates of response."

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"This PK profile of LY3009120 supports continued use of solid dispersion as the initial formulation for clinical development.Selective BRAF inhibitors vemurafenib and dabrafenib paradoxically activate downstream signaling, promote tumor growth in the WT BRAF cells, and are contraindicated for treatment of cancer patients whose tumors harbor a RAS mutation."

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"We analyzed 146 patients with BM from BRAF mutated melanoma treated with vemurafenib, dabrafenib, or dabrafenib+ trametinib between 2010 and 2016."

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"However, as reported for other BRAF inhibitors, dabrafenib also induced MAPK pathway activation in wild-type BRAF cells through CRAF (RAF1) signalling, potentially explaining the squamous cell carcinomas and keratoacanthomas arising in patients treated with BRAF inhibitors."

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"Data from four published datasets were analyzed to determine whether preexisting MEK1 (P124) mutations affect radiologic response or progression-free survival (PFS) in patients with BRAF (V600)-mutant metastatic melanoma treated with vemurafenib or dabrafenib."
Dabrafenib activates BRAF-V600E. 10 / 10
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"A total of 76 patients with BRAF V600E and 16 patients with V600K mutations were treated with dabrafenib 150 mg twice daily."

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"Improved survival in melanoma patients with BRAF V600E mutations treated with Vemurafenib and Dabrafenib shows promising results in the treatment of this devastating disease (Chapman et al., 2011; Hauschild et al., 2012)."

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"In our patient with an IDH wild-type epithelioid glioblastoma and a V600E mutation of the BRAF kinase treated with dabrafenib as salvage therapy, we achieved clinical and radiological stability over ten months, which is remarkable at that point of the clinical course with extensive pretreatment (XREF_FIG)."

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"Investigational nonchemotherapy options include moxetumomab pasudotox, which targets CD22; vemurafenib or dabrafenib, each of which targets the BRAF V600E protein; trametinib, which targets mitogen activated protein kinase enzyme (MEK); and ibrutinib, which targets Bruton tyrosine kinase (BTK)."

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"We report a case of a 35-year-old man with BRAF (V600E) metastatic melanoma treated with dabrafenib (as well as ipilimumab and whole brain radiotherapy), who is alive, 25 months after the onset of his DMC."

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"Interestingly, it was recently shown that the small molecule kinase inhibitor dabrafenib (Tafinlar) not only targets oncogenic mutant BRAF V600E but also potently inhibits CDK16 17 and that this mechanism may contribute to the efficacy of this drug against BRAF wild-type (WT) tumors 18."

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"In some studies, dabrafenib targeting of BRAF V600E decreased downstream phosphorylation of MEK and ERK [XREF_BIBR, XREF_BIBR]."

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"There is evidence regarding B-RAF inhibition activity in lung cancer, such as that reported in some case reports [XREF_BIBR, XREF_BIBR] and proved by interim analysis of a phase II trial, in which patients with BRAF V600E lung cancer beyond first line were treated with dabrafenib and obtained an ORR of 54% [XREF_BIBR]."

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"In a single case of BRAF V600E mutated NSCLC treated with dabrafenib, molecular profiling revealed three new acquired mutations in KRAS, TP53, and CDKN2A."

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"In this study, we report on the first case series of 3 patients with BRAF V600E mutated, malignant glioma and leptomeningeal disease successfully treated with dabrafenib."
Dabrafenib activates mutated BRAF. 10 / 10
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"We report a case of a patient with metastatic cutaneous BRAF mutant melanoma treated with dabrafenib who underwent repeat debulking surgery for a resistant lesion while disease in other metastatic sites was controlled."

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"Three (23%) were found positive for the presence of the BRAF mutation and were treated with the BRAF inhibitor dabrafenib."

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"Here, we show that when the human melanoma cell line A375SM (containing the active BRAF mutation) is treated with the BRAFi dabrafenib, P-ERK1/2 is significantly reduced, as expected, but Nodal expression is relatively unaffected (XREF_SUPPLEMENTARY)."

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"In response to the BRAF mutation, the patient was treated with dabrafenib (150mg) and trametinib (2mg) combination therapy in January 2018; after cycle 4 in April 2018, the CA-125 declined from 1186 to 102U/mL."

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"Dabrafenib and trametinib, used as single agents or in combination, have produced a significant improvement on the outcomes of patients with metastatic melanoma harboring BRAF mutations, and have changed the scope of treatment in this setting."

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"The immunomodulating CTLA-4 inhibitor ipilimumab is effective in some patients with asymptomatic and stable brain metastases, whilst the BRAF inhibitors vemurafenib and dabrafenib produce responses in BRAF mutant melanoma patients with symptomatic brain metastases."

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"Given the high response rate of BRAF V600E positive metastatic melanoma to mutant BRAF targeted inhibition by vemurafenib XREF_BIBR or dabrafenib XREF_BIBR, our observations also offer a rationale for future testing of BRAF targeted therapeutics for ameloblastoma."

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"Indeed, a second clinical grade RAF inhibitor, dabrafenib, effectively inhibits mutant BRAF signaling, elicits strong clinical responses in patients but also induces the formation of cuSCC/KA."

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"In a multicenter phase II trial, 172 patients with BRAF mutant melanoma with at least one asymptomatic brain metastasis were treated with dabrafenib."

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"An important approach to treatment for melanoma is the use of inhibitors such as vemurafenib, dabrafenib, or cobimetinib, which specifically target the mutant BRAF."
Dabrafenib activates BRAF-V600R. 2 / 2
| 2

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"The second patient had stage III BRAF V600R mutant melanoma that was treated with pembrolizumab and dabrafenib, and also developed a regressed melanocytic nevus."

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"Of note, a clinical report on patients with the BRAF V600R mutation who were treated with vemurafenib or dabrafenib has shown promise; however, the activity of BRAF inhibitors in other, more rare, BRAF mutations remains unknown."
Dabrafenib activates BRAF-V600K. 1 / 1
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"Unlike vemurafenib, which inhibits BRAF V600E and the RAF isoform CRAF with similar potency, dabrafenib is a more selective inhibitor of BRAF V600E and also targets the BRAF V600K mutant (lysine substitution for valine) that is detected in 7-20% of melanomas and causes activation of the MAPK pathway [43]."
Dabrafenib binds BRAF.
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"Dabrafenib bound to BRAF and ARAF with IC 50 of 6 and 26 nM, respectively, while its binding affinity to CRAF displayed an IC 50 of 150 nM, ~ 25-fold less than BRAF."

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"Comparison of the dabrafenib bound BRAF DeltaNVTAP and BRAF V600E structures reveals the overall kinase domain is largely unaffected (RMSD ~ 0.7 A), and the dimerization interface is preserved."

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"In contrast, as the dabrafenib binding mode requires the alphaC out conformation, dabrafenib binding to BRAF DeltaNVTAP results in significant local perturbation to the beta3-alphaC loop and alphaC."

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"For this purpose, we explored the interaction between dabrafenib and B-Raf."

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"A similar pattern of collective motions could be seen the BRAF and Dabrafenib complex (XREF_FIG)."

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"The most probable path in the Dabrafenib and BRAF complex (85% occupancy) could proceed from F595 of monomer A to the R-spine residues of the alphaC-helix (V504, L505), subsequently reaching to the interfacial residue R509 of the monomer A (XREF_FIG)."

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"The relatively high B factors for alphaC in all four copies of dabrafenib bound BRAF DeltaNVTAP in the asymmetric unit suggest that this region is less ordered than in the AZ-628- or sorafenib-BRAF DeltaNVTAP, or BRAF WT structures."

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"The small molecule inhibitors vemurafenib and dabrafenib selectively bind the active conformation of BRAF and inhibit signal transduction between BRAF and MEK."
Dabrafenib affects ERK
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Dabrafenib inhibits ERK.
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"More recently, it has been shown that the combination of dabrafenib and trametinib treatment decreased ERK activation, cell proliferation and induced apoptosis in human cancer cell lines harboring non V600 BRAF mutations, which accounts for approximately half of BRAF mutated NSCLC [XREF_BIBR]."

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"However, the triple combination dabrafenib, trametinib, and SHP099 markedly suppressed p (Y542) SHP2 (XREF_FIG) and ERK signaling (XREF_FIG) and growth (XREF_FIG) of RKO xenograft tumors, without any obvious effect on body weight (XREF_SUPPLEMENTARY), providing further evidence that combined ERK signaling and SHP2 inhibition may be an effective therapeutic strategy for patients with BRAF (V600E) colorectal tumors."

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"Thirty-fold higher concentrations of dabrafenib were required to inhibit ERK signaling in the latter compared with the former."

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"CRAF expression reduced Dabrafenib mediated ERK inhibition, but barely altered AZ628 mediated ERK inhibition."

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"A clinically relevant dose of Dabrafenib, a type I RAF-inhibitor, in HEK293T cells reduced ERK activity induced by BRAF mutations conferring high kinase activity in the presence and absence of CRAF."

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"Dabrafenib, an inhibitor of RAF-1 and B-RAF, suppressed the early activation of ERK, but a significant amount of phosphorylated ERK remained after 60min of shaking in the presence of dabrafenib (XREF_FIG A), which gradually increased over time only when FSS was applied (XREF_FIG C)."

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"Although both trametinib and dabrafenib blocked ERK1/2 activation in resistant cells, neither RAF and MEK inhibitor was able to effectively block cell proliferation, suggesting that the resistant cells were no longer RAF and MEK dependent."

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"Inhibitory effect of Dabrafenib on mutant BRAF induced ERK signaling."

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"Combination of Dabrafenib and Trametinib enhances and prolongs ERK inhibition in non V600 BRAF mutated cell lines."

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"30-fold higher concentrations of dabrafenib were required to inhibit ERK signaling in the latter compared to the former (XREF_FIG)."
Dabrafenib inhibits phosphorylated ERK. 4 / 4
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"Moreover, dabrafenib increased p-C-Raf and decreased p-MEK1/2 and p-ERK in both cell lines (XREF_FIG)."

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"In CRMM1, the lowest dose of Vemurafenib (0.4 muM) and Dabrafenib (0.005 muM) already inhibited p-ERK."

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"Importantly, TAS-116 and dabrafenib synergistically inhibited p-MEK1/2 and p-ERK (XREF_FIG)."

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"In contrast, in CM2005.1, increasing dosages of Vemurafenib and Dabrafenib decreased p-ERK gradually, while total ERK levels were not suppressed."
Dabrafenib activates ERK.
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"To further investigate the capacity of Dabrafenib and AZ628 to induce paradoxical ERK activation, we compared ERK activation between WT BRAF expressing, CRAF expressing, and WT BRAF and CRAF co-expressing HEK293T cells following 2 h AZ628 treatment."

medscan
"To explore this mechanistically, we profiled paradoxical ERK activation by vemurafenib, dabrafenib, encorafenib (LGX818), and PLX8394, demonstrating that vemurafenib induces ERK activation the greatest, while dabrafenib and encorafenib have higher "paradox indices", defined as the pERK activation EC80 divided by the IC80 against A375, corresponding to wider therapeutic windows for achieving tumor inhibition without paradoxical ERK activation."

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"In contrast, dabrafenib did not increase basal activity of MEK and ERK and efficiently suppressed light dependent activation of BRAF."

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"In addition, progression of a previously present KRAS mutated colon carcinoma due to stimulated ERK signaling was reported in a patient with a melanoma treated with dabrafenib [XREF_BIBR]."

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"In fact, both vemurafenib and dabrafenib actually increase MEK and ERK activation in the setting of RAS mutations."

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"In cells transfected with CRAF alone, Dabrafenib, but not AZ628, induced paradoxical ERK activation."

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"As before, dabrafenib and encorafenib stimulated ERK at lower levels,, at 3.90 +/- 0.34 and 4.04 +/- 0.16 fold above control, respectively."

medscan
"As before, dabrafenib and encorafenib stimulated ERK at lower levels, (Figure - ), at 3.90 ± 0.34 and 4.04 ± 0.16 fold above control, respectively (Figure - , Table )."

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"Conversely, in KRAS-mut contexts (MiaPaCa2 pancreatic cancer; A549 and A-427 NSCLC), EGFR family activation was dispensable for dabrafenib induced paradoxical ERK activation, as the addition of lapatinib to dabrafenib had no appreciable effect on ERK activation."

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"Dabrafenib induced significant phospho-MEK and -ERK activation at concentrations up to 1 muM and inhibited the phospho-MEK and -ERK at a high concentration of 10 muM."
Dabrafenib activates phosphorylated ERK. 4 / 4
| 4

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"Furthermore, to verify if MMP-9 may be involved in the mechanism of resistance to BRAF inhibitors A375 resistant cells were obtained and pERK protein levels showed opposite behavior compared to sensitive cells when treated with dabrafenib."

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"Although others have previously shown that RAF inhibitors paradoxically activate ERK signaling in wild-type BRAF and RAS mutated tumors [XREF_BIBR, XREF_BIBR - XREF_BIBR], we here confirmed that dabrafenib (1.25 to 2.5 muM) activated p-MEK1/2 and p-ERK in both cell lines, suggesting that paradoxical activation also occurs in MM (XREF_SUPPLEMENTARY)."

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"The pERK rebound was also elicited by dabrafenib, a more potent RAF inhibitor (XREF_SUPPLEMENTARY)."

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"Importantly, TAS-116 enhanced the inhibition of p-MEK1/2 or p-ERK induced by dabrafenib."
Dabrafenib phosphorylates ERK.
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Dabrafenib leads to the phosphorylation of ERK. 4 / 4
| 4

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"The BRAF inhibitors vemurafenib and dabrafenib were not able to inhibit phosphorylation of ERK, the downstream effector of the pathway, in primary cells."

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"Furthermore, MEK1 (P124Q/S) mutations were shown to have independent kinase activity and introduction of these mutations into a BRAF-mutant melanoma cell line diminished inhibition of ERK phosphorylation by dabrafenib and enhanced clonogenic survival in the presence of dabrafenib compared with cells ectopically expressing wild-type MEK1."

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"In HEK293T cells co-expressing WT BRAF and CRAF, Dabrafenib increased ERK phosphorylation (p-ERK) at all tested concentrations (8, 80, and 800 nM)."

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"In this case, dabrafenib did not inhibit but increased basal phosphorylation of MEK and ERK and further increased CRAF signaling induced by light exposure (XREF_FIG)."
Dabrafenib increases the amount of ERK.
| 4
Dabrafenib increases the amount of phosphorylated ERK. 4 / 4
| 4

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"In D594N BRAF and CRAF co-expressing HEK293T cells, both Dabrafenib and AZ628 treatment slightly increased p-ERK levels at 8 and 80 nM, and downregulated p-ERK at 800 nM."

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"Dabrafenib enhanced pERK expression levels and did not suppress human CD4 (+) or CD8 (+) T-cell function."

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"At low concentration ranges between 50nM and 1000nM, dabrafenib increased p-ERK1/2 levels accompanied with elevation of DR5 in three representative Ras-mutant cell lines (XREF_FIG)."

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"The model was an extension of the model of PC-12 (rat adrenal gland) cells [XREF_BIBR] and showed that increasing dabrafenib concentrations cause declining pERK levels but in unphysiological ranges."
Dabrafenib dephosphorylates ERK.
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Dabrafenib leads to the dephosphorylation of ERK. 4 / 4
| 4

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"Furthermore, our western blot analysis shows that phosphorylation of ERK, a major downstream target of BRAF, is inhibited in these cells by dabrafenib."

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"XREF_BIBR In vitro models have demonstrated that dabrafenib significantly decreases ERK phosphorylation, resulting in cell arrest in G1 phase and subsequent cell death."

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"18Both dabrafenib and trametinib inhibit ERK and MEK phosphorylation in other models of BRAF mutation positive melanoma."

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"45 Our results showed that vemurafenib and dabrafenib were not able to decrease levels of ERK phosphorylation significantly in mutated cases, although a slight effect was observed after dabrafenib treatment which could be an off-target effect."
Dabrafenib decreases the amount of ERK.
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Dabrafenib decreases the amount of phosphorylated ERK. 1 / 1
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"As expected, Dabrafenib treatment of HEK293T cells singly expressing BRAF mutants with elevated kinase activity led to decreased p-ERK1/2 levels."
Dabrafenib affects MAPK
| 19
Dabrafenib inhibits MAPK.
| 10
| 10

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"Dabrafenib is a reversible, ATP-competitive inhibitor that selectively inhibits BRAF V600E kinase; preclinical data indicate that dabrafenib inhibits the MAPK pathway in BRAF V600E mutated melanoma cells, leading to decreased proliferation and regression in xenograft models."

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"The MAPK pathway was inhibited by the BRAF inhibitor dabrafenib and the PI3K-AKT pathway was inhibited by the AKT inhibitor GSK2141795B (AKTi)."

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"Intraperitoneal daily delivery of BRAF V600E inhibitor dabrafenib only transiently suppressed MAPK signaling, and rather increased Akt signaling and failed to extend survival for mice with intracranial 2341 luc tumor."

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"Both Dabrafenib and Trametinib inhibit the MAPK pathway and are applied in the treatment of metastatic cutaneous melanoma."

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"In this paper, we use time-lapse, live-cell imaging, and single-cell analysis to show that BRAF-mutant melanoma cells exhibit time-variable and heterogeneous phenotypes when exposed to MAPK pathway inhibitors such as vemurafenib, dabrafenib, and trametinib near the IC 50 for cell killing."

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"MAPK pathway inhibitors -- including the RAF inhibitors vemurafenib and dabrafenib and the MEK inhibitor trametinib -- achieve clinicalbenefit in 80-90% ofBRAF V600 -mutant melanoma patients."

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"The mesopores of the nanoparticles were further loaded with small-molecule inhibitors, i. e., dabrafenib and trametinib, that target the hyperactive mitogen activated protein kinase (MAPK) pathway for melanoma treatment."

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"It is clear that the subset of melanoma patients with activating mutations in BRAF derive the most benefit from MAPK pathway inhibitors such as vemurafenib, dabrafenib, and trametinib, but individual patient responses are variable and, more importantly, transient due to the rapid development of resistance."

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"Like vemurafenib, dabrafenib downregulates activation of MAPK signaling."

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"Subsequent studies have demonstrated that the approved doses of both vemurafenib and dabrafenib produce a marked (> 90%) inhibition of MAPK pathway activation in biopsies of non CNS metastases."
Dabrafenib activates MAPK.
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"XREF_BIBR Surprisingly, the incidence of cutaneous squamous cell carcinoma was decreased on combination therapy compared with monotherapy using dabrafenib (7% versus 19%), possibly because MEK inhibition by trametinib attenuates dabrafenib induced paradoxical activation of the MAPK pathway in normal keratinocytes."

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"In light of the evidence that BRAF and MEK inhibitors have different effects on the MAPK pathway in BRAF wild-type cells, XREF_BIBR - XREF_BIBR it appears likely that trametinib attenuates dabrafenib induced activation of the MAPK pathway."

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"Examining our immunoblotting, cell cycle, and mutational profiling data collectively, we hypothesize that nucleotide pool depletion by competing cell signals of MTX induced ssDNA damage repair and dabrafenib induced MAPK pathway activation ultimately triggers cell death in BRAFi resistant MM cells."

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"Treatment with 10muM dabrafenib for two hours did not significantly increase CRAF and CRAF-CIBN expression but still led to slightly elevated MEK and ERK phosphorylation, indicating that the MAPK cascade activation by dabrafenib is not solely attributable to the CRAF protein level (XREF_FIG)."

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"In these contexts, MAPK activation was found to be dependent on EGFR family activation : indeed, the EGFR and HER2 inhibitor lapatinib strongly reduced dabrafenib induced MAPK activation."

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"Dabrafenib activates the MAPK pathway and disrupts MTX induced single-strand DNA damage repair causing apoptosis in acquired resistant MM cells."

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"However, as reported for other BRAF inhibitors, dabrafenib also induced MAPK pathway activation in wild-type BRAF cells through CRAF (RAF1) signalling, potentially explaining the squamous cell carcinomas and keratoacanthomas arising in patients treated with BRAF inhibitors."

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"Herein, we will focus on 4 recently published NEJM papers reporting the results of clinical trials, comprising 4 agents targeting the MAPK pathway : the BRAF inhibitors vemurafenib and dabrafenib, and the MEK inhibitors trametinib and cobimetenib."

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"We postulate that nucleotide pool depletion and ssDNA break induction by MTX may disrupt downstream transcriptional reprogramming activated by the dabrafenib induced MAPK pathway ultimately triggering cell death."
Y-27632 affects ROCK1
8 1 | 2 8
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eidos
"19 In vitro inhibition of ROCK1 by Y27632 leads to a reduction in the number of podosomes , reduced motility and phagocytosis , and an increased matrix degradation.18 ,20 RhoA also plays a role in the accumulation of macrophages in blood vessels ."

eidos
"The RhoA / Rho-kinase ( ROCK ) pathway is a key regulator of vascular function in health and disease.34 To understand if the impaired endothelial function was mediated by activation of ROCK signaling , we assessed endothelium-dependent relaxation in carotid arteries from male and female offspring in response to Y-27632 , which inhibits both ROCK1 and ROCK2 equally ."

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Y-27632 inhibits ROCK1. 8 / 8
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medscan
"Inhibition of ROCK1 and ROCK2 by Y-27632 significantly inhibits proliferation, migration, and invasion of laryngeal squamous cell carcinoma cells."

medscan
"This functional desensitization was blocked by the Rho kinase (ROCK) inhibitor, Y-27632, but not by Gq or Gs-pathway inhibitors or inhibition of β-arrestin recruitment."

medscan
"Y-27632, which selectively inhibits p160ROCK [ ], 3-Methyladenine, Bafilomycin A1, and Z-VAD-FMK were obtained from Calbiochem (San Diego, CA, USA)."

medscan
"Both a Rho inhibitor C3 exoenzyme and a Rho kinase (ROCK) inhibitor Y-27632 inhibited chemotaxis of rat basophilic leukemia-2H3 cells expressing human CCR1 cells toward CCL3, indicating that activation of the Rho/ROCK signaling pathway is required for the CCL3-mediated chemotaxis of the cells."

medscan
"Treatment with the Rho kinase (ROCK) inhibitor Y-27632 caused a decrease in human microlymphatic endothelial cells of dermal origin barrier function."

medscan
"Suppression of RhoA and Rho-kinase activities by anti-RhoA immunoglobulin G electroporation and Y-27632, respectively prevented morphologic changes and restored plasma membrane localization of occludin."

medscan
"We also found that the inhibition of ROCK1 by Y-27632 can inhibit the invasion and migration of gastric cells done at least, in part, by attenuating SRF expression."

medscan
"The objective of this study is to determine the effects of Rho-associated coiled-coil containing protein kinase (ROCK) inhibitor Y-27632 on the growth, invasion, and migration of Tca8113 and CAL-27 cells in tongue squamous cell carcinoma ."
1 |

drugbank
No evidence text available
Dabrafenib affects MPRIP
| 3 14
Dabrafenib inhibits MPRIP.
| 10
| 9

reach
"29 Dabrafenib inhibited RIP3 also 27-fold more potently than vemurafenib as determined by the luminescent assay (XREF_TABLE)."

reach
"Dabrafenib inhibits RIP3 independently of its effect on the B-Raf family members."

reach
"28 These data collectively indicate that (1) both RIP3 inhibition and B-Raf V600E inhibition are separable, (2) the biological outcomes of their inhibition are mutually independent and (3) dabrafenib inhibits RIP3 independently of its effect on the B-Raf family members."

reach
"On the other hand, only dabrafenib reversed TSZ induced necroptosis in RIP3 expressed HT29 cells, possibly because the other 2 B-Raf V600E inhibitors have significantly weak RIP3 inhibitory activity (XREF_TABLE)."

reach
"The B-Raf V600E inhibitor dabrafenib selectively inhibits RIP3 and alleviates acetaminophen induced liver injury."

reach
"Moreover, our data showed that dabrafenib inhibited RIP3 independently of its effect on the B-Raf family members."

reach
"The B-Raf inhibitor dabrafenib selectively inhibits RIP3 kinase activity by its ATP-competitive binding to the enzyme protein."

reach
"Selectivity analyses against the RIP family members revealed that dabrafenib inhibited RIP3 26600-, 38- and 14675-fold more potently than RIP1, RIP2 and RIP5, respectively (XREF_FIG)."

reach
"The human RIP3 inhibition by dabrafenib achieved similar effects to RIP3 deficiency in preventing acetaminophen induced hepatocyte necrosis 17 and ethanol caused liver injury 8 in mice."
Dabrafenib bound to ATP inhibits MPRIP. 1 / 1
| 1

reach
"By competitively binding of ATP to the enzyme protein dabrafenib inhibited RIP3 with high selectivity relative to other RIP family members."
Dabrafenib binds MPRIP.
| 3 4
| 3 4

reach
"We next investigated the possibility of the direct interaction between dabrafenib and RIP3."

reach
"For the docking study on the binding of dabrafenib to RIP3, we performed the homology modeling of human RIP3 based on the B-Raf crystal structure 3SKC."

medscan
"For the docking study on the binding of dabrafenib to RIP3, we performed the homology modeling of human RIP3 based on the B-Raf crystal structure 3SKC."

reach
"The data suggest that dabrafenib could directly bind to RIP3."

medscan
"The data suggest that dabrafenib could directly bind to RIP3."

reach
"Dabrafenib did not bind to the GST tag in the recombinant RIP3 protein (XREF_FIG, upper panel), excluding its influence on the assay for the binding of dabrafenib to RIP3."

medscan
"Dabrafenib did not bind to the glutathione S-transferase tag in the recombinant RIP3 protein ( , upper panel), excluding its influence on the assay for the binding of dabrafenib to RIP3."
| 16
Dabrafenib activates vemurafenib.
| 10

reach
"XREF_BIBR Keratic lesions occur in 12% patients treated with vemurafenib and in 8% treated with dabrafenib."

reach
"This is consistent with the slightly higher objective intracranial response rate seen in the phase II MBM study with dabrafenib compared to the phase II MBM study with vemurafenib, where the patient population treated with dabrafenib had fewer patients with> 4BMs (21% vs. 33%) XREF_BIBR, XREF_BIBR."

reach
"Photosensitivity sunburn is commonly seen in patients treated with vemurafenib but has not been reported in patients treated with dabrafenib."

reach
"For example, photosensitivity is common in patients treated with vemurafenib and much less frequent in patients treated with dabrafenib, whereas fever and chills are much more frequent with dabrafenib treatment."

reach
"Arthralgias are more common in patients treated with vemurafenib than in patients treated with dabrafenib; in 1 trial of vemurafenib, 53% of treatment-naive melanoma patients had arthralgias 76, and in 1 trial of dabrafenib, 27% of patients had arthralgias 120."

reach
"Sixty-seven patients were treated with vemurafenib, and 11 patients were treated with dabrafenib."

reach
"Patients treated with vemurafenib developed a cuSCC more quickly than those treated with dabrafenib (P =.048) (Fig 1, C)."

reach
"It has been observed in 6-19% XREF_BIBR, XREF_BIBR of patients treated with vemurafenib and 13% 44 of patients treated with dabrafenib."

reach
"SCCs and keratoacanthomas were detected in approximately 20-30% of patients in the trials of vemurafenib, and approximately 10% of patients treated with dabrafenib [XREF_BIBR, XREF_BIBR]."

reach
"Among the 22 patients, 11 were subjected to dabrafenib or vemurafenib monotherapy, whereas 3 were treated with dabrafenib alone for 8, 5 or 4 months and then with dabrafenib plus trametinib."
| 4

reach
"After four cycles of carboplatin and pemetrexed the CT showed no response, switch to docetaxel is planned at the time of the writing of this report.We computed a 3-dimensional structure model of BRAF G469L, which suggested impaired binding of vemurafenib and dabrafenib, providing a theoretical explanation for the clinical course of our patient."

reach
"Both vemurafenib and dabrafenib inhibit mutant BRAF by binding to the ATP binding pocket that in the setting of mutant BRAF monomers potently inhibit RAF/MEK/ERK signaling."

reach
"In preclinical studies, there is strong evidence for the interaction of vemurafenib, dabrafenib, trametinib, palbociclib, cobimetinib and omipalisib with P-gp and BCRP."

reach
"Three-dimension structural modeling of BRAF G469L suggested that it induces a conformational change impairing the binding of vemurafenib and dabrafenib."
| 2

reach
"Reduction in circulating tumor DNA (ctDNA) BRAF level is associated with tumor regression by RECIST : maximum ctDNA BRAFV600 level reduction occurs in Cycle 2 and 3 time points in vemurafenib treated patients and in at least Cycle 4 in patients treated with the combination of dabrafenib and trametinib."

reach
"For most BRAF mutated melanoma patients and particularly those with a high tumor load, vemurafenib or other BRAF inhibitors such as dabrafenib are the treatment of choice."

reach
"et al found that AEB071 at high doses (5muM) induced apoptosis in 92-1, mel202 and omm1.3 uveal melanoma cell lines, which harbor GNAQ mutations."

reach
"These results indicate that AEB071 selectively induced apoptosis in UM cells harboring GNAQ mutations."

reach
"AEB071 induced apoptosis is associated with decreased expression of antiapoptotic proteins, yet the underlying molecular mechanisms remain to be revealed."

reach
"The combination of AEB071 and the PI3Kalpha inhibitor BYL719 synergistically inhibited proliferation and induced apoptosis in GNAQ- and GNA11-mutant cell lines 102 and is being investigated in a phase Ib trial in metastatic uveal melanoma [ClinicalTrials.gov identifier : NCT02273219]."

reach
"Furthermore, we demonstrated that the PKC inhibitor sotrastaurin induced cell apoptosis and cell cycle arrest in DLBCL cells potentially through regulating the expression of MCT-1."

reach
"We next examined whether AEB071 promoted apoptosis in UM cells."

reach
"AEB071 and BYL719 combination induces apoptosis."

reach
"Unlike former PKC inhibitors, AEB071 did not enhance apoptosis of murine T-cell blasts in a model of activation induced cell death."

reach
"Interestingly, targeting PKC and BTK at the same time led to ibrutinib mediated rescue of a weak sotrastaurin induced apoptosis in MINO cells."

reach
"This is important since higher concentrations of AEB071 are known to cause cell cycle perturbations and apoptosis in certain cell types."

reach
"A selective PKC inhibitor, sotrastaurin, effectively inhibited cell proliferation and induced cell apoptosis in a dose- and time dependent manner."

reach
"Finally, neither NAC nor AEB071 inhibited cellular apoptosis maximally."

sparser
"Finally, neither NAC nor AEB071 inhibited cellular apoptosis maximally (Figure xref )."

reach
"Expression of PIM-1L-wildtype or -S65D reduced sotrastaurin mediated apoptosis and growth inhibition in MV4-11 transfectants."
Y-27632 affects ROCK2
9 1 | 1 2 1
Y-27632 inhibits ROCK2.
9 1 | 1 2
9 | 1

tas
No evidence text available

tas
No evidence text available

tas
No evidence text available

tas
No evidence text available

eidos
"The RhoA / Rho-kinase ( ROCK ) pathway is a key regulator of vascular function in health and disease.34 To understand if the impaired endothelial function was mediated by activation of ROCK signaling , we assessed endothelium-dependent relaxation in carotid arteries from male and female offspring in response to Y-27632 , which inhibits both ROCK1 and ROCK2 equally ."

tas
No evidence text available

tas
No evidence text available

tas
No evidence text available

tas
No evidence text available

tas
No evidence text available
Y-27632 inhibits ROCK2. 2 / 2
| 2

medscan
"Furthermore, Y-27632, an inhibitor of ROCK2, attenuated the Angiotensin II-induced contraction of human airway smooth muscle cells by blocking the RhoA/ROCK2 signaling pathway which is involved in this contraction, and thus may be a major regulator involved in the basal maintenance of contractility in human airway smooth muscle cells."

medscan
"Inhibition of ROCK1 and ROCK2 by Y-27632 significantly inhibits proliferation, migration, and invasion of laryngeal squamous cell carcinoma cells."
1 |

drugbank
No evidence text available
Y-27632 activates ROCK2.
| 1
Y-27632 activates ROCK2. 1 / 1
| 1

reach
"Furthermore, Y-27632, an inhibitor of ROCK2, attenuated the Ang II-induced contraction of HASMCs by blocking the RhoA/ROCK2 signaling pathway which is involved in this contraction, and thus may be a major regulator involved in the basal maintenance of contractility in HASMCs."
Dabrafenib affects RAF1
1 | 13
Dabrafenib inhibits RAF1.
1 | 6
1 | 6

reach
"XREF_BIBR At higher concentrations, dabrafenib also inhibits wild-type BRAF and CRAF kinases and other kinases such as salt inducible kinase 1 (SIK1), NIMA related kinase 11 (NEK11), and LIM domain kinase 1 (LIMK1)."

reach
"Dabrafenib also inhibits wild type BRAF and CRAF kinases."

tas
No evidence text available

reach
"The IC50 of Dabrafenib to inhibit CRAF is ~ 10-fold less than that of Vemurafenib [XREF_BIBR - XREF_BIBR]."

reach
"Therefore it is likely that dabrafenib, at high concentration ranges, inhibits c-Raf, resulting in blockage of c-Raf-dependent ERK activation and subsequent DR5 upregulation."

reach
"At higher concentrations dabrafenib inhibited CRAF signaling."

reach
"Dabrafenib enhanced activity of light stimulated CRAF at low dose and inhibited CRAF signaling at high dose."
Dabrafenib activates RAF1.
| 4
Dabrafenib activates phosphorylated RAF1. 3 / 3
| 3

reach
"Western blot analysis showed that TAS-116 markedly inhibited p-C-Raf, which was paradoxically activated by dabrafenib in U266 MM cells (XREF_FIG)."

reach
"Moreover, dabrafenib increased p-C-Raf and decreased p-MEK1/2 and p-ERK in both cell lines (XREF_FIG)."

reach
"Moreover, TAS-116 markedly inhibited p-C-Raf or p-Akt, which were paradoxically activated by dabrafenib in the U266 MM cell line."
| 1

reach
"Dabrafenib enhanced activity of light stimulated CRAF at low dose and inhibited CRAF signaling at high dose."
Dabrafenib phosphorylates RAF1.
| 2
Dabrafenib leads to the phosphorylation of RAF1 on S338. 2 / 2
| 2

reach
"We observed that Dabrafenib treatment of all HEK293T transfectants resulted in phosphorylation of the transfected CRAF molecule at S338, irrespective of the presence and type of BRAF molecule."

reach
"As expected, Dabrafenib treatment increased CRAF S338 phosphorylation, while AZ628 treatment only slightly elevated CRAF S338 phosphorylation."
Dabrafenib increases the amount of RAF1.
| 1
Dabrafenib increases the amount of RAF1. 1 / 1
| 1

reach
"Already at a concentration of 1muM, dabrafenib elevated the protein level of the light-insensitive constructs CRAF and CRAF-CIBN, higher concentrations tested up to 10muM further increased their protein level (XREF_FIG)."
| 13
Dabrafenib activates trametinib.
| 8

reach
"XREF_BIBR Preliminary findings from another trial that combined dabrafenib and trametinib versus dabrafenib with ipilimumab found that several patients treated with the combination of dabrafenib and trametinib with ipilimumab had an increased incidence of colonic perforation."

reach
"5-7 Two additional agents, the BRAF inhibitor dabrafenib and the mitogen activated protein kinase inhibitor trametinib have recently been approved (both in the USA, and dabrafenib in the European Union)."

reach
"Median PFS was improved by 3.6 months in patients receiving dabrafenib concurrently with a 2 mg/day dose of trametinib when compared to patients only being treated with dabrafenib."

reach
"Five patients received two different targeted regimens, including four patients treated with vemurafenib followed by dabrafenib plus trametinib, and one patient treated with dabrafenib followed by dabrafenib plus trametinib."

reach
"Of note, the duration of the interval between first BRAFi and rechallenge in the 3 patients who achieved CR from the rechallenge spanned from 5.9 months (a patient who had first-line dabrafenib) to 20.8 months (a patient who had first-line dabrafenib plus trametinib), while in patients who had PD as rechallenge best response the interval of BRAFi drugs was from 0.9 (dabrafenib plus trametinib as first BRAFi) to 24.6 months (a patient treated with dabrafenib as first BRAFi)."

reach
"Additional compounds and antibodies for targeted, immuno- as well as combination therapy have been and are currently being developed such as the BRAF V600mut inhibitor dabrafenib [XREF_BIBR], mitogen activated protein kinase kinase (MEK) inhibitors trametinib [XREF_BIBR] and cobimetinib [XREF_BIBR], the anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody ipilimumab [XREF_BIBR] as well as anti-programmed cell death protein 1 (PD-1) antibodies pembrolizumab [XREF_BIBR] and nivolumab [XREF_BIBR]."

reach
"8-10 Patients treated with the combination of dabrafenib plus trametinib significantly increased overall survival compared with those treated with dabrafenib (hazard ratio [HR] 0.63; 95% CI 0.42-0.94, p = 0.02) 8 or another BRAF inhibitor, vemurafenib, 9 alone (0.69; 0.53-0.89, p = 0.005)."

reach
"A Case of Intracranial Hemorrhage Caused by Combined Dabrafenib and Trametinib Therapy for Metastatic Melanoma."
| 3

reach
"Furthermore, in H1299 (NRAS-mut lung adenocarcinoma), in which combined treatment was clearly synergistic (CI : 0.13), enforced expression of different KRAS isoforms (G12C, G12D, G12V) did not substantially modify the nature of pharmacologic interactions between dabrafenib and trametinib, which remained synergistic in all KRAS-mut clones, although to a slightly lesser extent in H1299 V9 (KRAS G12V, CI : 0.73, Fig."

reach
"In preclinical studies, there is strong evidence for the interaction of vemurafenib, dabrafenib, trametinib, palbociclib, cobimetinib and omipalisib with P-gp and BCRP."

reach
"However, synergism analysis across the entire set of cellular models analyzed displayed no significant correlation between RAS mutational status and synergistic interactions between dabrafenib and trametinib."
| 2

reach
"It is predictive for inhibition by combined Dabrafenib and Trametinib treatment [XREF_BIBR] and is itself targetable by novel agents."

reach
"Despite strong Dabrafenib antagonization of Trametinib, co-treatment always resulted in ERK inhibition compared to the vehicle group."
Sotrastaurin affects GNAQ
| 13
Sotrastaurin inhibits GNAQ.
| 7
| 5

reach
"These findings together suggest that AEB071 suppressed growth of GNAQ mutated UM cells via inhibition of multiple PKC isoforms."

reach
"AEB071 inhibits cell proliferation in GNAQ and GNA11-mutant Uveal Melanoma cell lines with inhibition of the PKC/ERK1/2 pathway."

reach
"AEB071 at low micromolar concentrations significantly decreased viability of all three GNAQ mutated cell lines (XREF_FIG)."

reach
"The PKC inhibitors AEB071 and AHT956 selectively inhibit the growth of GNAQ or GNA11 mutant melanoma cell lines."

reach
"In the present study we describe the first small molecule inhibitor that selectively exhibits antiproliferative activity of UM cells harboring GNAQ mutations : the novel PKC inhibitor AEB071 reduced viability of GNAQ mutated UM cell lines, but had little effect on those carrying wild type GNAQ."
Sotrastaurin inhibits mutated GNAQ. 2 / 2
| 2

reach
"These findings together indicate that AEB071 selectively inhibited NF-kappaB activation in UM cells harboring GNAQ mutations."

reach
"Importantly, we demonstrate that AEB071 selectively repressed NF-kappaB activation in UM cells harboring GNAQ mutations and this is accompanied by downregulation of multiple PKC isoforms, in particular PKCalpha, PKCdelta, and PKCepsilon."
Sotrastaurin activates GNAQ.
| 6
| 3

reach
"Treatment with 2 and 5 muM AEB071 for 72 hours significantly increased Annexin V positive (apoptotic) populations in GNAQ mutated 92.1 and Omm1.3 cells (XREF_FIG)."

reach
"In contrast, AEB071 did not increase Annexin V positive cell populations or caspase-3 cleavage in UM cells harboring wild type GNAQ (XREF_FIG)."

reach
"To test this hypothesis, UM cells carrying wild type GNAQ or GNAQ mutated at codon 209 were treated with the PKC inhibitor AEB071 (sotrastaurin), a PKC inhibitor that has potent activity against classical and novel PKC isotypes."
Sotrastaurin activates mutated GNAQ. 3 / 3
| 3

reach
"These results indicate that AEB071 selectively induced apoptosis in UM cells harboring GNAQ mutations."

reach
"To test this hypothesis, uveal melanoma cells harboring wild-type or mutant GNAQ were treated with the PKC inhibitor AEB071 (sotrastaurin) or infected with lentivirus expressing short hairpin RNAs (shRNA) targeting PKC isoforms."

reach
"To test this hypothesis, UM cells harboring wild type or mutant GNAQ were treated with the PKC inhibitor AEB071 (sotrastaurin) or infected with lentivirus expressing shRNAs targeting PKC isoforms."
| 1 1 10
| 1 1 8

reach
"Vemurafenib, encorafenib and dabrafenib induce cell cycle arrest and apoptosis in BRAF melanoma cell lines; however, a residual population of tumor cells survive."

reach
"Using thyroid cancer, melanoma, and colon cancer cell models, we showed that dabrafenib and trametinib induced robust apoptosis of cancer cells harboring both BRAF V600E and TERT promoter mutations but had little proapoptotic effect in cells harboring only BRAF V600E."

eidos
"Vemurafenib , encorafenib and dabrafenib induce cell cycle arrest and apoptosis in BRAF melanoma cell lines ; however , a residual population of tumor cells survive ."

reach
"In COLO205 cells, SHR8443, trametinib and dabrafenib individually induced apoptosis, and the combination of SHR8443 and trametinib and dabrafenib showed enhanced apoptosis induction."

reach
"We show that TAS-116 induced synergistic anti-MM cytotoxicity and enhanced dabrafenib induced apoptosis in RAS mutated MM cell lines."

reach
"Although SHR8443 alone did not induce noticeable apoptosis in A375 cells, it enhanced the apoptosis induced by trametinib or dabrafenib."

reach
"In addition, annexin V/PI staining showed that TAS-116 significantly enhanced apoptosis induced by dabrafenib in the U266 MM cell line (P < 0.001 in the combination treatment versus TAS-116 monotherapy; P < 0.01 in the combination treatment versus dabrafenib monotherapy) (XREF_FIG)."

reach
"Dabrafenib and trametinib in BRAF V600E/K, and trametinib in BRAF wild-type tumor cells induced apoptosis markers, upregulated HLA molecule expression, and downregulated certain immunosuppressive factors such as PD-L1, IL1, IL8, NT5E, and VEGFA."

reach
"The combined administration of a SAMMSON specific ASO and dabrafenib, a BRAF inhibitor, induced apoptosis in the PDTX model, whereas administration of dabrafenib alone only inhibited tumor growth."

medscan
"Combined treatment with dabrafenib and AKTi increases the subG1 fraction and induces apoptosis in cell lines sensitive to AKTi as single agent."

reach
"We have shown that at clinically relevant doses, vemurafenib, but not dabrafenib, potently inhibits JNK signaling and suppresses apoptosis, which cooperates with paradoxical ERK activation to induce tumors [XREF_BIBR]."

reach
"More recently, it has been shown that the combination of dabrafenib and trametinib treatment decreased ERK activation, cell proliferation and induced apoptosis in human cancer cell lines harboring non V600 BRAF mutations, which accounts for approximately half of BRAF mutated NSCLC [XREF_BIBR]."
Y-27632 affects ROCK
| 3 2 6 1
Y-27632 inhibits ROCK. 7 / 7
| 1 6

medscan
"To investigate the effects of the Rho-dependent protein kinase (ROCK) inhibitor Y-27632 on the kinetics of E-cadherin, F-actin, and Oct3/4 distributions in dissociated human embryonic stem cells and to analyze their interactions morphologically, Y-27632-treated [R(i) (+)] and untreated [R(i) (-)] cells were immunohistochemically stained for E-cadherin and Oct3/4 within 24h of dissociation and also for F-actin."

medscan
"Rho kinase inhibition by Y-27632 prevented CTGF and hydroxyproline, whereas the RhoA activator CN03 increased CTGF expression."

medscan
"Together these results indicate that Y-27632 inhibits ROCK in Clear Cell Renal Cell Carcinoma and selectively targets Von Hippel Lindau-deficient Clear Cell Renal Cell Carcinoma while sparing Von Hippel Lindau-reconstituted Clear Cell Renal Cell Carcinoma in multiple genetic backgrounds."

medscan
"However, Y-27632, a specific inhibitor of the protein kinase ROCK, significantly blocked apoptosis induced by phosphorylated FKHRL1 thr-32 (P < 0.01), which was mediated by L-NMMA."

medscan
"Since Y-27632 inhibits both ROCK family members: ROCK1 and ROCK2, we sought to determine which ROCK was responsible for the synthetic lethal effect."

medscan
"In vitro, we also found that blockade of Rho kinase with inhibitor Y-27632 prevented high-glucose-induced loss of megalin expression and an increase of transforming growth factor-β(1), thereby increasing the absorption rate of FITC-labeled albumin by tubular epithelial cells."

trips
"Inhibition of ROCK by Y27632 suppressed the c-FLIPL-promoted motility by reducing phosphorylation of FAK and ERK."
Y-27632 inhibits ROCK. 5 / 5
| 3 1 1

eidos
"Rho kinase inhibition by Y-27632 decreased aldosterone induced CTGF upregulation ( 52 + / -15 % ) ."
| PMC

trips
"Inhibition of ROCK by Y-27632 inhibited the activity of RhoA and promoted the apoptosis."

eidos
"Notably , inhibition of RhoA and ROCK by Tat-C3 and Y27632 , respectively , enhanced neurite outgrowth ( Fig. 3A ) [ [ 17 ] , [ 18 ] , [ 19 ] ] ."

eidos
"As previously demonstrated in other cell types , nocodazole treatment triggered a global increase of RhoA activity and myosin light chain ( MLC ) phosphorylation ( Liu et al ., 1998 ; Takesono et al ., 2010 ; Fig. S2 , d and e ) , and pharmacological inhibition of the effector kinase Rho-associated protein kinase ( ROCK ) by Y27632 reverted this effect ."

reach
"Enteroids, when required, were digested into 349 single cells using TrypLE and seeded into collagen-coated transwells (0.33cm 2 , 0.4μm 350 pore size, Polycarbonate, Fisher #07-200-147) in ROCK Inhibitor Y-27632 supplemented 351 maintenance media in 24-well plates."
| DOI
Sotrastaurin affects PKC
| 1 4 7
Sotrastaurin inhibits PKC.
| 1 4 5
| 1 4 5

reach
"AEB-071 (AEB) is a specific inhibitor of protein kinase C, which prevents T-lymphocyte activation."

sparser
"Furthermore, inhibition of PKC by AEB071 significantly eliminated CCL2-induced elevated Nav1.8 currents."

reach
"These results indicate that AEB071 inhibits PKC signaling in vivo, but that compensatory mechanisms prevent the suppression of the MAP-kinase pathway and that the treatment is not sufficient to completely stop cell proliferation or kill cells."

reach
"These findings demonstrate AEB071 induced selective inhibition of the PKC and MAPK pathway in UM cells carrying GNAQ mutations."

medscan
"These data further support the importance of protein kinase Cθ kinase activity in the oncogenic activity of triple-negative breast cancer cells, and the potential for clinical translation of protein kinase Cθ kinase inhibitors as a therapeutic option for patients with triple-negative breast cancer.Fig. 6Treatment with AEB071 inhibits protein kinase C θ activity and impairs growth of triple-negative breast cancer cells. a MDA-231-Luc-D3H2LN cells were treated with AEB071 at the indicated concentrations for 24 hours."

sparser
"In the present study, we found that the inhibition of PKC by AEB071 significantly reduced the CCL2-induced Na v 1.8 peak current densities, and the in vitro PKC kinase assays also confirmed that PKC contributed to the phosphorylation of Na v 1.8 in response to CCL2."

reach
"Combining two drugs may be useful as sotrastaurin mainly inhibits the PKC and NF-kappaB pathway, while TAC has a strong effect on the calcineurin and NFAT pathway and as it now seems also inhibits, though to a certain extent, the NF- kappaB pathway."

reach
"Furthermore, inhibition of PKC by AEB071 significantly eliminated CCL2 induced elevated Nav1.8 currents."

sparser
"However, the viral transcriptional activators HBx and PreS2-activator large surface protein have both been reported to trigger signaling processes involving PKC so that an anti-viral effect of PKC-inhibition by sotrastaurin would also be plausible xref , xref , xref ."

sparser
"In cell-free kinase assays AEB071 inhibited PKC, with K(i) values in the subnanomolar to low nanomolar range."
Sotrastaurin dephosphorylates PKC.
| 1
Sotrastaurin leads to the dephosphorylation of PKC. 1 / 1
| 1

reach
"To determine if PKC activation was related to ERK phosphorylation, we treated cells with the PKC inhibitor AEB071 that inhibits PKC phosphorylation induced by PMA (4beta-phorbol 12-myristate 13-acetate), a specific activator of PKC."
Sotrastaurin activates PKC.
| 1
| 1

reach
"We found that miR-196a knockdown or PKC inhibition by sotrastaurin changed PKC expression which then reduced esophageal cancer cell proliferation and downregulated proliferating cell nuclear antigen expression via the classical B-cell receptor-PKC nuclear factor-kappaB pathway but not the alternative pathway; in addition, miR-196a inhibition can increase the caspase level and induce esophageal cancer cell apoptosis."

reach
"35 The BRAF inhibitors Vemurafenib or Dabrafenib suppress proliferation of BRAF mutated melanoma cells, 36 but surprisingly Dabrafenib effectively suppresses RIPK3 activity as an off-target effect."

reach
"In contrast to these compounds, the B-Raf V600E inhibitor dabrafenib selectively decreased proliferation of BRAF-mutant cell clones."

reach
"Increased potency of encorafenib results in IC50 values of 40nmol/l or less in the majority of melanoma cell lines, whereas higher concentrations of dabrafenib (< 100nmol/l), and especially vemurafenib (< 1mumol/l) are necessary to inhibit proliferation of most cell lines [XREF_BIBR **]."

reach
"We observed that the combination of vemurafenib or dabrafenib with TH1579 significantly reduced cell proliferation and induced cell death (p < 0.01) in A375, A375VR4, and ESTDAB049 cell lines compared with either treatment alone."

reach
"More recently, it has been shown that the combination of dabrafenib and trametinib treatment decreased ERK activation, cell proliferation and induced apoptosis in human cancer cell lines harboring non V600 BRAF mutations, which accounts for approximately half of BRAF mutated NSCLC [XREF_BIBR]."

reach
"XREF_BIBR The combination of dabrafenib with the PI3K and mTOR inhibitor decreased cell proliferation in both parental and resistant cell lines and offers a potential alternative treatment strategy in patients with acquired dabrafenib resistance."

medscan
"RAF inhibitors such as vemurafenib and dabrafenib block BRAF-mediated cell proliferation and achieve meaningful clinical benefit in the vast majority of patients with BRAF(V600E)-mutant melanoma. 46999999="V600E"}"

reach
"While dabrafenib decreases cancer cell proliferation by inhibiting the oncogene BRAF V600E within tumor cells XREF_BIBR, pembrolizumab functions by increasing the immune systems T-cell response to tumor antigens XREF_BIBR."

reach
"Co-treatment of both A100 and dabrafenib significantly suppressed in vitro cell proliferation and three- dimensional (3D) matrigel growth."

reach
"Here we provide evidence that the combination of dabrafenib and AKTi synergistically inhibits proliferation in the majority of cell lines tested."

reach
"Nevertheless, our in vitro study indicates that vemurafenib and dabrafenib can be counterproductive as therapeutics by inducing paradoxical activation of the MAP-kinase signaling pathway, thereby increasing cell proliferation."
Dabrafenib bound to recombinant hPXR activates cell population proliferation. 1 / 1
| 1

reach
"We also showed that dabrafenib binds to recombinant hPXR, induces the expression of hPXR responsive genes in colon LS174T-hPXR cancer cells and human hepatocytes and finally increases the proliferation in LS174T-hPXR cells."

sparser
"Consistent with previous findings of selective regulation of T-cell development in PKC-θ − / − animal model, AEB071 inhibited TCR/CD28-mediated T-cell proliferation, GvHD and allograft rejection ( xref – xref ), but retained T-cell antiviral response ( xref )."

reach
"Additionally, AEB071 attenuates BCR mediated survival pathways, inhibits CpG induced survival and proliferation of CLL cells in vitro, and effectively blocks microenvironment mediated survival signaling pathways in primary CLL cells."

medscan
"These results indicate that AEB071 inhibits protein kinase C signaling in vivo, but that compensatory mechanisms prevent the suppression of the MAP-kinase pathway and that the treatment is not sufficient to completely stop cell proliferation or kill cells."

reach
"Like the combination of AEB071 + RAD001, combination of AEB071 and CGM097 further blocked cell proliferation compared to single agent treatment in most GNAQ/11 mutated cell lines."

eidos
"90 This reduction might be related to inhibition of cell proliferation by AEB071 ."

reach
"Preclinical studies demonstrated that sotrastaurin (AEB071) and enzastaurin, two adenosine triphosphate-competitive selective inhibitors of PKCbeta, induce apoptosis and inhibit the proliferation of BCR-subtypes of ABC-DLBCL in vitro and in vivo [XREF_BIBR, XREF_BIBR]."

reach
"Drug screening in leukemia cell lines revealed that sotrastaurin (a PKC inhibitor) suppressed the proliferation of the FLT3-ITD-positive AML cell line MV4-11 but not of K562, HL60, or KG-1a cells, similar to SGI-1776 (a PIM-1 and FLT3 inhibitor) and quizartinib (an FLT3 inhibitor)."

reach
"Preclinical studies demonstrated that sotrastaurin (AEB071) and enzastaurin, two adenosine triphosphate-competitive selective inhibitors of PKCbeta, induce apoptosis and inhibit the proliferation of BCR-subtypes of ABC-DLBCL in vitro and in vivo [XREF_BIBR, XREF_BIBR]."

reach
"Consistent with previous findings of selective regulation of T-cell development in PKC-theta - / - animal model, AEB071 inhibited TCR and CD28 mediated T-cell proliferation, GvHD and allograft rejection, but retained T-cell antiviral response."

reach
"The combination of AEB071 and the PI3Kalpha inhibitor BYL719 synergistically inhibited proliferation and induced apoptosis in GNAQ- and GNA11-mutant cell lines 102 and is being investigated in a phase Ib trial in metastatic uveal melanoma [ClinicalTrials.gov identifier : NCT02273219]."

reach
"A selective PKC inhibitor, sotrastaurin, effectively inhibited cell proliferation and induced cell apoptosis in a dose- and time dependent manner."
| 11
| 10

reach
"Importantly, we demonstrate that AEB071 selectively repressed NF-kappaB activation in UM cells harboring GNAQ mutations and this is accompanied by downregulation of multiple PKC isoforms, in particular PKCalpha, PKCdelta, and PKCepsilon."

reach
"Sotrastaurin inhibited the NF-kappaB dependent cytokine production in the T cell subsets by 88.5%, 85.7%; and 88.0% respectively (p < 0.01 compared to no drug; XREF_FIG)."

reach
"Furthermore, the PKC-theta inhibitor AEB071 inhibits NFkappaB and NFAT but not AP1 activity XREF_BIBR."

reach
"Sotrastaurin inhibited NF-kappaB activation in the respective T cell subsets by 93%, 95% and 86% (p < 0.01 vs. no drug), while mycophenolic acid did not affect this activation pathway."

reach
"These findings together indicate that AEB071 selectively inhibited NF-kappaB activation in UM cells harboring GNAQ mutations."

reach
"AEB071 selectively inhibits NF-kappaB activity in GNAQ mutated UM cells."

reach
"Sotrastaurin, a PKC-Theta inhibitor, was utilized to block NF-kappaB activation following TCR engagement, and was found to significantly inhibit TCR mediated chemotherapy resistance in T8ML-1 and in most primary TCL cells (XREF_SUPPLEMENTARY)."

reach
"The downregulation of these PKC isoforms may contribute to AEB071 suppression of NF-kappaB activity."

reach
"To confirm the involvement of PI3Kdelta and PKCbeta in the resistance to ATO, we first studied whether idelalisib and sotrastaurin inhibited the activation of Akt, NF-kappaB and STAT3."

reach
"Combining two drugs may be useful as sotrastaurin mainly inhibits the PKC and NF-kappaB pathway, while TAC has a strong effect on the calcineurin and NFAT pathway and as it now seems also inhibits, though to a certain extent, the NF- kappaB pathway."
Sotrastaurin dephosphorylates NFkappaB.
| 1
Sotrastaurin leads to the dephosphorylation of NFkappaB. 1 / 1
| 1

reach
"Moreover, idelalisib and sotrastaurin, specific inhibitors for PI3Kdelta and PKCbeta, respectively, inhibited Akt phosphorylation, NF-kappaB and STAT3 activation and Mcl-1 upregulation, and rendered cells sensitive to ATO."
Momelotinib affects JAK2
1 1 | 3 6
Momelotinib inhibits JAK2.
1 1 | 3 5
1 1 | 3 5

eidos
"Since tylophorine arrested IkappaBalpha mRNA , reduced IkappaBalpha protein expression , and liberated p65 ( Figs 2B , C and 5 ) , the diminishment of p65 phosphorylation via JAK2 inhibition by CYT387 ( Figs 2B-c and 6A ) was reasoned to be capable of working in an additive manner with tylophorine for anti-TGEV activity ( Figs 3 and 4 ) ."

reach
"The addition of momelotinib suppressed paclitaxel induced JAK2 and STAT3 pathway activation in ovarian cancer cell lines."

reach
"However, the discontinuation of paclitaxel and momelotinib treatment no longer suppressed JAK2 and STAT3 activation and CSC like development, thus allowing the resumption of tumor growth and dissemination."

reach
"Momelotinib is a potent inhibitor of JAK1 and JAK2 that demonstrated efficacy in patients with primary and secondary myelofibrosis."

signor
No evidence text available

reach
"Momelotinib is a potent inhibitor of JAK1 and JAK2."

tas
No evidence text available

eidos
"We also found that JAK2 inhibition by CYT387 not only inhibited NF-kappaB activation ( p65 phosphorylation ) and subsequent cytokine production , e.g ."

eidos
"JAK2 inhibition either by CYT387 ( a JAK family inhibitor ) or by silencing JAK2-expression revealed a dominant JAK2 mediated p65 phosphorylation pathway for NF-kappaB activation and resulted in NF-kappaB inhibition , which overrode the IkappaBalpha regulation via the IKK-2 ."

reach
"28 Finally, momelotinib (also known as CYT-387) inhibits both JAK1 (IC 50 11 nm) and JAK2 (IC 50 18 nm), rather than JAK3 (IC 50 0.16 muM), although off-target effects (serine/threonine kinase IKBKE) have been described."
Momelotinib activates JAK2.
| 1
| 1

reach
"Significant inhibition of JAK2 and STAT3 activation by 1muM momelotinib in both HEY and TOV21G cell lines was demonstrated by Western blot and immunofluorescence (XREF_SUPPLEMENTARY)."

reach
"Dabrafenib mediated necroptosis suppression strongly correlated with its inhibitory effect on MLKL phosphorylation."

reach
"Here, Dabrafenib blocks necroptosis by interference with RIPK3 mediated MLKL phosphorylation."

reach
"However, dabrafenib did not ease apoptosis induced by TNFalpha plus Smac mimetic (TS) in HT29 cells (XREF_SUPPLEMENTARY), 4 further indicating that dabrafenib specifically inhibited the necroptosis pathway."

reach
"Geserick et al. [XREF_BIBR] reported that Dabrafenib, a V600E- or V600K mutated porto-oncogene serine/threonine protein kinase B-RAF, inhibited necroptosis in melanoma cells whenever RIPK3 is present."

reach
"Interestingly, recent studies have shown that the B-RAF V600E inhibitor dabrafenib has a function to selectively inhibit RIPK3 and prevents necroptosis in various disease models."

reach
"On the other hand, only dabrafenib reversed TSZ induced necroptosis in RIP3 expressed HT29 cells, possibly because the other 2 B-Raf V600E inhibitors have significantly weak RIP3 inhibitory activity (XREF_TABLE)."

reach
"XREF_BIBR Importantly, dabrafenib directly inhibits RIP3 kinase activity, in addition to TNF-alpha and NO induced necroptosis of keratinocytes."

reach
"Dabrafenib can inhibit necroptosis of human hepatocytes incubated with APAP."

medscan
"Moreover, only dabrafenib rescued cells from RIP3-mediated necroptosis induced by the necroptosis-induced combinations, that is, tumor necrosis factor (TNF)α, TNF-related apoptosis-inducing ligand or Fas ligand plus Smac mimetic and the caspase inhibitor z-VAD."

medscan
"Here, Dabrafenib blocks necroptosis by interference with RIPK3-mediated MLKL phosphorylation."

reach
"Furthermore, the inhibitor of mutant BRAF Dabrafenib, but not Vemurafenib, inhibited necroptosis in melanoma cells whenever RIPK3 is present."
| 11
Dabrafenib activates autophagy.
| 10

reach
"Additionally, dabrafenib caused autophagy in melanoma and this autophagic process was regulated by miR-26a via modifying HMGB1 expression."

reach
"We treated the melanoma cell lines A375 and MEL624 with dabrafenib in the presence or absence of autophagy inhibitors, 3-methyladenosine, to determine if inhibition of autophagy induced by dabrafenib will affect the viability of melanoma cells to the drug."

reach
"Dabrafenib induces both autophagy and ER stress in a dose dependent pattern in melanoma cells."

reach
"In this study, first, we want to investigate whether dabrafenib can cause autophagy in two melanoma cell lines; second, whether this autophagy induced by dabrafenib is regulated by ER stress; and third, whether blocking ER stress and autophagy can increase the efficacy of dabrafenib in treating melanoma cells."

reach
"In addition, autophagy signaling is also impaired by knocking down PERK, which supports our notion that dabrafenib induced autophagy is regulated by ER stress (XREF_FIG)."

reach
"Our data demonstrated that autophagy was induced by dabrafenib in a dose dependent pattern and targeting dabrafenib induced autophagy overcame the drug resistance in melanoma cells."

reach
"Taken together, we verified that dabrafenib triggers both autophagy and ER stress in both B-Raf inhibitor sensitive and B-Raf inhibitor resistant melanoma cells."

reach
"Autophagy induced by dabrafenib protects the melanoma cells from the cytotoxicity of dabrafenib."

reach
"Dabrafenib induced autophagy by downregulation of miR-26a following upregulation of HMGB1 in melanoma [XREF_BIBR]."

reach
"Furthermore, silencing HMGB1 inhibited autophagy induced by dabrafenib in melanoma cells."
Dabrafenib inhibits autophagy.
| 1

reach
"Our data demonstrated that autophagy was induced by dabrafenib in a dose dependent pattern and targeting dabrafenib induced autophagy overcame the drug resistance in melanoma cells."
1 | 10
Dabrafenib inhibits Melanoma.
1 | 9

medscan
"The selective RAF inhibitors Vemurafenib (PLX4032) and GSK2118436 are clinically available and effective in melanomas with activating mutations in BRAF ( )."

medscan
"Both vemurafenib and dabrafenib have significant clinical response in patients with BRafV600E/K melanoma ( , , )."

medscan
"BRAF kinase inhibitors, such as PLX4032 and GSK-2118436, have shown anti-tumor activities in melanoma patients with BRAF mutations ( ; ; )."

medscan
"While it is clear that BRAF inhibitor induce cutaneous squamous cell carcinoma with varying efficiency, it is unknown why this is the case, even though the most extensively tested inhibitors, vemurafenib and dabrafenib, appear to have similar efficacy in melanoma [ , - ]."

medscan
"Recent clinical trials clarified that combined MEK (trametinib) and BRAF (dabrafenib) inhibition is effective molecular-targeted therapy for melanoma patients harbouring BRAF mutation, suggesting that the RSK-EphA2 pathway inhibition affects the therapeutic efficacy ."

medscan
"While tumor mutation status is critical to outcomes of melanoma patients treated with selective BRAF inhibitors PLX4032 , and GSK2118436, its predictive significance for other therapies is largely unknown."

medscan
"The development of targeted inhibitors, vemurafenib and dabrafenib, has led to improved clinical outcome for melanoma patients with BRAFV600E mutations."

medscan
"The development of targeted inhibitors, vemurafenib and dabrafenib, has led to improved clinical outcome for melanoma patients with BRAFV600Emutations."

medscan
"RAF inhibitors such as vemurafenib and dabrafenib block BRAF-mediated cell proliferation and achieve meaningful clinical benefit in the vast majority of patients with BRAF(V600E)-mutant melanoma. 46999999="V600E"}"

ctd
No evidence text available
Dabrafenib activates Melanoma.
| 1
| 1

medscan
"The introduction into the clinical practice of vemurafenib and dabrafenib, potent inhibitors of BRAFV600 mutants, makes the assessment of BRAF mutations as a crucial step toward the appropriate use of a targeted melanoma treatment."
Dabrafenib affects MEK
| 11
Dabrafenib inhibits MEK.
| 5
| 3

reach
"As such, the combination of BRAF plus MEK inhibition by dabrafenib plus trametinib appears to be an improvement on single-agent BRAF inhibition."

reach
"This has implications for combination treatment strategies in melanoma where BRAF and MEK kinase inhibitors such as dabrafenib and trametinib may make melanoma cells less permissive of TVEC viral replication and cellular lysis."

reach
"AZ628 or Dabrafenib plus Trametinib enhanced MEK and ERK inhibition compared to single treatments."
Dabrafenib inhibits phosphorylated MEK. 2 / 2
| 2

reach
"Moreover, dabrafenib increased p-C-Raf and decreased p-MEK1/2 and p-ERK in both cell lines (XREF_FIG)."

reach
"Importantly, TAS-116 and dabrafenib synergistically inhibited p-MEK1/2 and p-ERK (XREF_FIG)."
Dabrafenib activates MEK.
| 4
Dabrafenib activates phosphorylated MEK. 2 / 2
| 2

reach
"Importantly, TAS-116 enhanced the inhibition of p-MEK1/2 or p-ERK induced by dabrafenib."

reach
"Although others have previously shown that RAF inhibitors paradoxically activate ERK signaling in wild-type BRAF and RAS mutated tumors [XREF_BIBR, XREF_BIBR - XREF_BIBR], we here confirmed that dabrafenib (1.25 to 2.5 muM) activated p-MEK1/2 and p-ERK in both cell lines, suggesting that paradoxical activation also occurs in MM (XREF_SUPPLEMENTARY)."
| 2

reach
"In fact, both vemurafenib and dabrafenib actually increase MEK and ERK activation in the setting of RAS mutations."

reach
"In contrast, dabrafenib did not increase basal activity of MEK and ERK and efficiently suppressed light dependent activation of BRAF."
Dabrafenib phosphorylates MEK.
| 2
Dabrafenib leads to the phosphorylation of MEK. 2 / 2
| 2

reach
"18Both dabrafenib and trametinib inhibit ERK and MEK phosphorylation in other models of BRAF mutation positive melanoma."

reach
"In this case, dabrafenib did not inhibit but increased basal phosphorylation of MEK and ERK and further increased CRAF signaling induced by light exposure (XREF_FIG)."

reach
"We describe a patient who presented vitreous infiltration of a cutaneous melanoma, who was effectively treated with dabrafenib."

reach
"However, it abrogated up-regulation of ECM invasion induced by dabrafenib in this cell line."

reach
"Moreover, both agents completely abrogated dabrafenib induced stimulation of ECM invasion."
| PMC

reach
"Moreover, although dabrafenib still stimulated invasiveness in PTTG1 silenced A375R cells, ECM invasion by those cells was significantly reduced as compared to that of drug treated PTTG1 expressing cells."

reach
"These results indicated that dabrafenib, when combined with pmel-1 ACT and IL-2, increases macrophage and Tregs infiltration in the tumor microenvironment, thus providing a potential mechanism for the suboptimal antitumor effect with this combination."

reach
"Moreover, although 4 muM LEE011 did not affect A375R basal invasiveness, it abrogated stimulation of ECM invasion induced by dabrafenib in this cell line."

reach
"In both cell lines, inhibition of invasiveness induced by dabrafenib alone was higher than that caused by PTTG1 silencing alone and similar to that induced by dabrafenib plus siPTTG1."

reach
"Dabrafenib treatment markedly impaired ECM invasion in A375 and SK-Mel28 cells transfected with either siCTRL or siPTTG1."

reach
"PTTG1 silencing also impaired proliferation and invasiveness of A375R and SK-Mel28R cells, and counteracted dabrafenib induced stimulation of ECM invasion in A375R cells."

reach
"A375 and A375R cells differently responded to dabrafenib, which strongly inhibited invasiveness and VEGF-A secretion in A375 cells, whereas it stimulated these functions in A375R cells."
| PMC
Sotrastaurin affects ERK
| 1 9
Sotrastaurin dephosphorylates ERK.
| 7
Sotrastaurin leads to the dephosphorylation of ERK. 7 / 7
| 7

reach
"AEB071 selectively decreases Erk1/2 phosphorylation in UM cells harboring GNAQ mutations."

reach
"We observed that the PKC inhibitor AEB071 inhibited ERK phosphorylation and cellular apoptosis in addition to PKC phosphorylation."

reach
"Further, AEB071 (PKC inhibitor) and NAC (ROS scavenger) inhibited both ERK phosphorylation and caspase-3 activation."

reach
"This is consistent with previous reports indicating that AEB071 inhibits ERK1/2 phosphorylation in GNAQ mutant cell lines."

reach
"The ERK1/2 phosphorylation response to capsaicin was similarly suppressed by sotrastaurin."

reach
"However, AEB071 only significantly inhibited Erk1/2 phosphorylation in GNAQ mutant cells while it had minimal effect on Akt phosphorylation in both GNAQ wild type and mutated cells (XREF_FIG)."

reach
"AEB071 inhibited Erk1/2 phosphorylation in GNAQ mutated but not GNAQ wild type UM cells, and had minimal impact on Akt phophorylation."
Sotrastaurin inhibits ERK.
| 1 2
Sotrastaurin inhibits phosphorylated ERK. 2 / 2
| 1 1

sparser
"Our studies indicate that both AEB071 and BYL719 can inhibit p-ERK as single agents or as part of combination therapy."

reach
"Our studies indicate that both AEB071 and BYL719 can inhibit p-ERK as single agents or as part of combination therapy."
| 1

reach
"This was supported by our data that whereas the PKC inhibitor AEB071 inhibited G69-250-induced ERK and caspase-3 activation fully, the ROS scavenger NAC had no effect."
4 | 1 1 3
4 | 1 1 3

medscan
"These data further support the importance of protein kinase Cθ kinase activity in the oncogenic activity of triple-negative breast cancer cells, and the potential for clinical translation of protein kinase Cθ kinase inhibitors as a therapeutic option for patients with triple-negative breast cancer.Fig. 6Treatment with AEB071 inhibits protein kinase C θ activity and impairs growth of triple-negative breast cancer cells. a MDA-231-Luc-D3H2LN cells were treated with AEB071 at the indicated concentrations for 24 hours."

tas
No evidence text available

sparser
"Similar to genetic PKCtheta depletion, pharmacological PKCtheta inhibition by the PKC-selective inhibitor AEB071 (Sotrastaurin) [ xref ] significantly reduced the killing capacity of S. typhimurium -infected wild-type Mφ (Fig.  xref )."

reach
"AEB071 blocks the catalytic activity of PKCalpha, PKCbeta and PKCtheta isoforms at a low picomolar concentration range, as well as PKCdelta, PKCepsilon and PKCetaat higher, nanomolar, concentrations [XREF_BIBR]."

tas
No evidence text available

tas
No evidence text available

tas
No evidence text available

reach
"In agreement with these findings, PKCtheta was activated by EGF, insulin, and FBS, and the PKC inhibitor Sotrastaurin impaired the activation of PKCtheta and TBK1 (XREF_FIG and XREF_FIG, XREF_FIG)."

reach
"AEB071 inhibits not only PKCtheta, but also other novel (Ca 2+ -independent delta, epsilon, and eta; nPKC) and conventional (Ca 2+ -dependent alpha and beta; cPKC) members at sub-nanomolar to low nanomolar concentrations, with a 1,000-10,000-fold lower selectivity for other kinases."

reach
"We first examined whether p53 reactivation (Nutlin-3) in combination with PKC inhibition (Sotrastaurin) synergistically inhibits the growth of UM cells."

reach
"These findings suggest that NF-kappaB activity is critically important for UM cells and its suppression contributes to AEB071 induced growth inhibition of UM cells harboring GNAQ mutations."

reach
"The PKC inhibitor AEB071 selectively inhibits growth of UM cells harboring GNAQ mutations."

reach
"Notably, AEB071 at low micromolar concentrations significantly inhibited the growth of UM cells harboring GNAQ mutations through induction of G1 arrest and apoptosis."

reach
"AEB071 selectively inhibited the growth of UM cells harboring GNAQ mutations by targeting PKC/Erk1/2 and PKC and NF-kappaB pathways."

reach
"Similarly, AEB071 decreased GSK3beta Ser9 phsophorylation in all UM cell lines studied here (XREF_SUPPLEMENTARY)."

reach
"Metastatic UM patients (n = 153) were treated with AEB071 in a Phase I, single-arm study."

reach
"To test this hypothesis, UM cells harboring wild type or mutant GNAQ were treated with the PKC inhibitor AEB071 (sotrastaurin) or infected with lentivirus expressing shRNAs targeting PKC isoforms."

reach
"In contrast, AEB071 did not increase Annexin V positive cell populations or caspase-3 cleavage in UM cells harboring wild type GNAQ (XREF_FIG)."
Dabrafenib affects RIPK3
| 4 5
Dabrafenib inhibits RIPK3.
| 4 4
| 4 4

medscan
"Our data suggest that loss of RIPK3 in melanoma and selective inhibition of the RIPK3/MLKL axis by BRAF inhibitor Dabrafenib, but not Vemurafenib, is critical to protect from necroptosis."

reach
"Indeed, the B-RAF inhibitor Dabrafenib has recently been shown to inhibit RIP3 independently of its effect on the B-RAF family members [XREF_BIBR]."

reach
"In contrast to vemurafenib, it has been shown that dabrafenib inhibited RIPK3 activity in an ATP-competitive manner, and irrespectively of inhibition of BRAF mut [XREF_BIBR, XREF_BIBR]."

medscan
"The BRAF inhibitors Vemurafenib or Dabrafenib suppress proliferation of BRAF-mutated melanoma cells, but surprisingly Dabrafenib effectively suppresses RIPK3 activity as an off-target effect."

medscan
"Dabrafenib decreased the RIP3-mediated Ser358 phosphorylation of mixed lineage kinase domain-like protein (MLKL) and disrupted the interaction between RIP3 and MLKL."

medscan
"Consistent with another recent study, Dabrafenib also interfered with RIPK3 activity in our study ( and ) and was able to block necroptosis and, to some extent, apoptosis."

reach
"Since the B-RAF inhibitor Dabrafenib has recently been reported to inhibit RIP3 by its adenosine-5 '-triphosphate (ATP)-competitive binding to the enzyme [XREF_BIBR], we also tested the effect of Dabrafenib on the induction of necroptosis in AML cells."

reach
"54 The B-Raf V600E inhibitors Vemurafenib and Dabrafenib inhibit RIPK3, with Dabrafenib being effective in the submicromolar range."
Dabrafenib binds RIPK3.
| 1

reach
"B-Raf inhibitor dabrafenib binds to RIP3 in a cell-free system, but the low potency hinders its application in treating necroptosis involving diseases XREF_BIBR, XREF_BIBR."
Sotrastaurin affects activation
| 8
Sotrastaurin inhibits activation. 8 / 8
| 8

sparser
"Sotrastaurin inhibits T-cell activation by peptide–MHC and CD28 co-stimulation in a PKC-dependent manner () and is currently in clinical trials for liver transplantation () and renal transplantation ()."

sparser
"This was supported by our data that whereas the PKC inhibitor AEB071 inhibited G69-250-induced ERK and caspase-3 activation fully, the ROS scavenger NAC had no effect (Figure xref )."

sparser
"This was to ensure that any AEB071 that would inhibit T responder cell activation was transferred along with the treated cells."

sparser
"Sotrastaurin inhibited NF-κB activation in the respective T cell subsets by 93%, 95% and 86% (p<0.01 vs. no drug), while mycophenolic acid did not affect this activation pathway."

sparser
"However, the finding that the combined deletion of PKCθ and PKCα primarily affects NFAT activation ( xref ) is inconsistent with findings that AEB071 does not inhibit NFAT activation ( xref )."

sparser
"Sotrastaurin inhibits T-cell activation by peptide–MHC and CD28 co-stimulation in a PKC-dependent manner ( xref ; xref ) and is currently in clinical trials for liver transplantation ( xref ) and renal transplantation ( xref )."

sparser
"AEB071 inhibits early T-cell activation via a calcineurin inhibitor independent pathway and is currently investigated as a therapeutic agent to prevent allograft rejection after renal transplantation."

sparser
"These findings together indicate that AEB071 selectively inhibited NF-κB activation in UM cells harboring GNAQ mutations."

reach
"Tacrolimus did not alter the pharmacokinetics of sotrastaurin; however, sotrastaurin increased tacrolimus area under the concentration-time curve by 2.0-fold (90% confidence interval, 1.8-2.1)."

reach
"Tacrolimus exposure was significantly increased by sotrastaurin in the initial weeks posttransplant by a pharmacokinetic interaction."

reach
"In clinical trials, it is recommended that patients administer sotrastaurin consistently either with or without food to avoid food-related fluctuations in drug exposure over time.157Clinical drug interaction studies to date have demonstrated that sotrastaurin increases the area under the concentration–time curve of everolimus (1.2-fold) and of tacrolimus (2-fold).158 Sotrastaurin increased tacrolimus concentration inasmuch as the tacrolimus dose needed to achieve a given C0 was up to 47% lower when combined with sotrastaurin versus MMF.158 Conversely, sotrastaurin area under the concentration–time curve is increased up to 1.8-fold by cyclosporine and 4.6-fold by ketoconazole.159PKC is a family of serine/threonine-specific protein kinases involved in diverse signal transduction pathways that modulate a whole range of cellular processes, including activation, proliferation, differentiation, apoptosis, and autophagy.160 PKC-θ has been shown to be essential in the T cell receptor/CD3 signal transduction pathway."
| PMC

reach
"28 In these lines, it has been recently reported that tacrolimus does not alter the pharmacokinetics of sotrastaurin; however, sotrastaurin increases tacrolimus area under the concentration-time curve by twofold."

reach
"Sotrastaurin increased tacrolimus concentrations by a pharmacokinetic interaction inasmuch as the tacrolimus dose needed to achieve a given C0 was up to 47% lower when combined with sotrastaurin versus with MPA."

reach
"In clinical trials, it is recommended that patients administer sotrastaurin consistently either with or without food to avoid food-related fluctuations in drug exposure over time.123Clinical drug interaction studies to date have demonstrated that sotrastaurin increases the area under the concentration–time curve of everolimus (1.2-fold) and of tacrolimus (2-fold).124 Sotrastaurin increased tacrolimus concentration inasmuch as the tacrolimus dose needed to achieve a given C0 was up to 47% lower when combined with sotrastaurin versus MMF.124 Conversely, sotrastaurin area under the concentration–time curve is increased up to 1.8-fold by cyclosporine and 4.6-fold by ketoconazole.125PKC is a family of serine/threonine-specific protein kinases involved in diverse signal transduction pathways that modulate a whole range of cellular processes, including activation, proliferation, differentiation, apoptosis, and autophagy.231 PKC-θ has been shown to be essential in the T-cell receptor/CD3 signal transduction pathway."
| PMC

reach
"124 Sotrastaurin increased tacrolimus concentration inasmuch as the tacrolimus dose needed to achieve a given C 0 was up to 47% lower when combined with sotrastaurin versus MMF."
| PMC

reach
"158 Sotrastaurin increased tacrolimus concentration inasmuch as the tacrolimus dose needed to achieve a given C 0 was up to 47% lower when combined with sotrastaurin versus MMF."
| PMC
| 1 6
| 1 3

medscan
"Dabrafenib selectively inhibits cell viability in B-RafV600E mutant cancer cells."

reach
"Dabrafenib selectively inhibits cell viability in B-Raf V600E mutant cancer cells."

reach
"Whereas increasing doses of PLX4032 or dabrafenib or E2F1 depletion alone reduced cell viability, combination of BRAF and E2F1 inhibition resulted in increased cell death in BRAF mutant lines."

reach
"Through cell viability analysis, flow cytometry, sphere forming, and western blot analysis, we found that the dabrafenib can synergize with cetuximab to reduce cell viability, induce enhanced apoptotic rates and cell cycle arrest in BRAF (V600E)-mutant HT-29 cells and inhibits stem cell capacities."
| 3

reach
"The result showed that dabrafenib reversed the reduction of the HT29 cell viability induced by TRAIL or Fas ligand plus Smac mimetic and z-VAD (SZ; XREF_FIG)."

reach
"We harvested and examined cell viability by the Cell Counting Kit-8 and found that the group treated with only dabrafenib was more resistant to the drug in comparison to the group that was cotreated with 4-phenylbutyrate."

reach
"BRAF inhibitor treatment alone suppressed cell survival more effectively than radiation in all the mutant V600E BRAF cell lines, and vemurafenib, but not dabrafenib, also inhibited cell survival in the WT BRAF cell lines at clinically relevant concentrations."
Dabrafenib affects CDK16
1 | 6
Dabrafenib inhibits CDK16.
1 | 5
1 | 5

reach
"Interestingly, it was recently shown that the small molecule kinase inhibitor dabrafenib (Tafinlar) not only targets oncogenic mutant BRAF V600E but also potently inhibits CDK16 17 and that this mechanism may contribute to the efficacy of this drug against BRAF wild-type (WT) tumors 18."

reach
"The ability of dabrafenib to inhibit CDK16 was demonstrated by the ability of the vemurafenib-CDK16 siRNA combination to mimic the effects of dabrafenib on pRB and p27."

reach
"However, given that dabrafenib and rebastinib are not specific inhibitors of CDK16, the identification or development of CDK16 selective inhibitors may be necessary."

tas
No evidence text available

reach
"Rebastinib and dabrafenib are potent inhibitors of CDK16."

reach
"3.6 Dabrafenib mediated CDK16 inhibition enhances the cell cycle effects of NEK9 inhibition."
Dabrafenib binds CDK16.
| 1

reach
"We also found that the binding of CDK16 to dabrafenib and rebastinib was mutually exclusive with its binding to the cyclin Y/14-3-3 complex."
A-674563 affects AKT1
5 | 2
A-674563 inhibits AKT1.
5 |
5 |

tas
No evidence text available

tas
No evidence text available

tas
No evidence text available

tas
No evidence text available

tas
No evidence text available
A-674563 increases the amount of AKT1.
| 1
A-674563 increases the amount of AKT1. 1 / 1
| 1

reach
"A-674563 also increased p-AKT-1 and p-AKT-2 expression in the A549 cells and increased expression over time in the A427 cells."
A-674563 dephosphorylates AKT1.
| 1
A-674563 leads to the dephosphorylation of AKT1. 1 / 1
| 1

reach
"To determine the specific inhibition of A-674563 on Akt-1, we examined the phosphorylation status of GSK-3beta, a well characterized substrate of Akt isoforms, since A-674563 does not inhibit Akt-1 phosphorylation, but blocks the downstream targets in a dose dependent manner."
Sotrastaurin affects growth
| 1 5
Sotrastaurin inhibits growth. 6 / 6
| 1 5

sparser
"AEB071, an inhibitor of PKCθ kinase activity, also inhibits growth and invasive branching of TNBC cells in 3-D cultures, further supporting a role for PKCθ kinase activity in triple-negative cancer cell growth."

medscan
"These data further support the importance of protein kinase Cθ kinase activity in the oncogenic activity of triple-negative breast cancer cells, and the potential for clinical translation of protein kinase Cθ kinase inhibitors as a therapeutic option for patients with triple-negative breast cancer.Fig. 6Treatment with AEB071 inhibits protein kinase C θ activity and impairs growth of triple-negative breast cancer cells. a MDA-231-Luc-D3H2LN cells were treated with AEB071 at the indicated concentrations for 24 hours."

sparser
"AEB071 selectively inhibited the growth of UM cells harboring GNAQ mutations by targeting PKC/Erk1/2 and PKC/NF-κB pathways."

sparser
"The PKC inhibitor AEB071 selectively inhibits growth of UM cells harboring GNAQ mutations."

sparser
"The PKC inhibitors AEB071 and AHT956 selectively inhibit the growth of GNAQ or GNA11 mutant melanoma cell lines."

sparser
"AEB071 inhibits GNAQ Q209L -mediated tumor growth in vivo."
Momelotinib affects JAK1
1 2 | 3
1 2 | 3

tas
No evidence text available
| DOI

signor
No evidence text available

tas
No evidence text available

reach
"28 Finally, momelotinib (also known as CYT-387) inhibits both JAK1 (IC 50 11 nm) and JAK2 (IC 50 18 nm), rather than JAK3 (IC 50 0.16 muM), although off-target effects (serine/threonine kinase IKBKE) have been described."

reach
"Momelotinib is a potent inhibitor of JAK1 and JAK2 that demonstrated efficacy in patients with primary and secondary myelofibrosis."

reach
"Momelotinib is a potent inhibitor of JAK1 and JAK2."

reach
"We then assessed the dabrafenib induced ER stress response in both A375 and MEL624 cells."

reach
"Taken together, we verified that dabrafenib triggers both autophagy and ER stress in both B-Raf inhibitor sensitive and B-Raf inhibitor resistant melanoma cells."

reach
"Dabrafenib induces both autophagy and ER stress in a dose dependent pattern in melanoma cells."

reach
"Therefore, our current studies support that dabrafenib induced ER stress can further activate autophagy and, therefore, provide multiple potential targets in the ER stress-autophagy link in melanoma treatment."

reach
"Based on the fact that dabrafenib induces ER stress response in melanoma cells, we then tried to determine whether ER stress induced by dabrafenib will protect the cancer cells from the cytotoxicity of the drug."

reach
"In our study on melanoma, we found that dabrafenib can induce ER stress and further activate autophagy."
Dabrafenib affects CYP3A4
| 1 5
| 1 5

reach
"As dabrafenib is a moderate inducer of CYP3A4 and all NNRTIs are substrates, NNRTIs are unlikely to reduce dabrafenib concentrations."

eidos
"Because dabrafenib induces CYP3A4 and CYP2C9 it decreased the systemic exposures of the CYP3A4 substrate midazolam , the CYP2C9 substrate S-warfarin , and the CYP3A4 / CYP1A2 substrate R-warfarin ."
| PMC

reach
"Because dabrafenib induces CYP3A4 and CYP2C9 it decreased the systemic exposures of the CYP3A4 substrate midazolam, the CYP2C9 substrate S-warfarin, and the CYP3A4/CYP1A2 substrate R-warfarin.XL281 (BMS-908662) is a highly selective inhibitor of B-RAF and C-RAF, but not A-RAF."
| PMC

reach
"Because dabrafenib induces CYP3A4 and CYP2C9 it decreased the systemic exposures of the CYP3A4 substrate midazolam, the CYP2C9 substrate S-warfarin, and the CYP3A4/CYP1A2 substrate R-warfarin."
| PMC

reach
"Dabrafenib induces CYP3A4 and thus may alter the metabolism of other medications metabolized through this pathway by reducing the bioavailability of substrates."

reach
"Combined P-gp and strong CYP3A4 inducers such as carbamazepine, St John 's wort, dabrafenib, rifampin, and phenytoin can potentially decrease the anticoagulant efficacy of apixaban, so their combination with apixaban should be avoided."
| 2 4
Sotrastaurin inhibits MARCKS.
| 2 3
| 2 3

reach
"In these cells AEB071 inhibited p-MARCKS and p-S6 but induced activation of p-AKT over time, which was inhibited by BYL719 in the combination therapy."

reach
"AEB071 inhibited p-MARCKS, a PKC substrate, and pS6 in all the cell lines, independently of the mutational status."

sparser
"In these cells AEB071 inhibited p-MARCKS and p-S6 but induced activation of p-AKT over time, which was inhibited by BYL719 in the combination therapy."

sparser
"AEB071 inhibited p-MARCKS, a PKC substrate, and pS6 in all the cell lines, independently of the mutational status."

reach
"In all models, GNAQ/11 mutated and wt, AEB071 treatment led to decreased pMARCKS and pPKCdelta."
Sotrastaurin dephosphorylates MARCKS.
| 1
Sotrastaurin leads to the dephosphorylation of MARCKS. 1 / 1
| 1

reach
"In the GNAQ-mutant cells, AEB071 decreased phosphorylation of MARCKS, a substrate of PKC, along with ERK1/2 and ribosomal S6, but persistent AKT activation was present."
Sotrastaurin affects ACE2
| 2 4
Sotrastaurin inhibits ACE2.
| 2 3
| 2 3

reach
"∗P < 0.01 vs. 0, 2, 4, and 7.8 mM; ∗∗P < 0.05 vs. 0 and 2 mM; †P < 0.05 vs. 0 mM; n = 5.FIGURE 2: The pan-PKC inhibitor sotrastaurin reduces ACE2 shedding in mouse proximal tubular cells."

reach
"On the other hand, sotrastaurin (10-5 M) completely inhibited ACE2 shedding under conditions of high D-glucose (28 mM), to levels observed under basal conditions, with or without TAPI-1 (Figure 2C)."

reach
"On the other hand, sotrastaurin (10 -5 M) completely inhibited ACE2 shedding under conditions of high D-glucose (28 mM), to levels observed under basal conditions, with or without TAPI-1."

sparser
"In cells maintained in 7.8 mM D -glucose, ACE2 shedding was significantly inhibited by the pan-protein kinase C (PKC) competitive inhibitor sotrastaurin, but not by an inhibitor of ADAM17."

sparser
"In cells maintained in 7.8 mM D-glucose, ACE2 shedding was significantly inhibited by the pan-protein kinase C (PKC) competitive inhibitor sotrastaurin, but not by an inhibitor of ADAM17."
Sotrastaurin activates ACE2.
| 1
| 1

reach
"* P < 0.01 vs. 0, 2, 4, and 7.8 mM; * * P < 0.05 vs. 0 and 2 mM; † P < 0.05 vs. 0 mM; n = 5.The pan-PKC inhibitor sotrastaurin reduces ACE2 shedding in mouse proximal tubular cells."
Momelotinib affects STAT3
| 6
Momelotinib inhibits STAT3.
| 5
| 5

reach
"Conversely, momelotinib (JAK inhibitor) effectively inhibited STAT3 activation in A549 cells."

reach
"The addition of momelotinib suppressed paclitaxel induced JAK2 and STAT3 pathway activation in ovarian cancer cell lines."

reach
"The addition of daily momelotinib to weekly paclitaxel treatment significantly inhibited the JAK2 and STAT3 activation and CSC like phenotypes in mice tumors."

reach
"However, the discontinuation of paclitaxel and momelotinib treatment no longer suppressed JAK2 and STAT3 activation and CSC like development, thus allowing the resumption of tumor growth and dissemination."

reach
"However, momelotinib effectively inhibited STAT3 activation suggesting that JAK-2 activation plays an important role in STAT3 activation in A549 cells."
Momelotinib activates STAT3.
| 1
| 1

reach
"Significant inhibition of JAK2 and STAT3 activation by 1muM momelotinib in both HEY and TOV21G cell lines was demonstrated by Western blot and immunofluorescence (XREF_SUPPLEMENTARY)."

reach
"Moreover, both agents completely abrogated dabrafenib induced stimulation of ECM invasion."
| PMC

reach
"In both siCTRL and A375R and siPTTG1 and A375R cells, exposure to dabrafenib promoted ECM invasion."

reach
"However, it abrogated up-regulation of ECM invasion induced by dabrafenib in this cell line."

reach
"Moreover, although 4 muM LEE011 did not affect A375R basal invasiveness, it abrogated stimulation of ECM invasion induced by dabrafenib in this cell line."

reach
"PTTG1 silencing also impaired proliferation and invasiveness of A375R and SK-Mel28R cells, and counteracted dabrafenib induced stimulation of ECM invasion in A375R cells."

reach
"Dabrafenib treatment markedly impaired ECM invasion in A375 and SK-Mel28 cells transfected with either siCTRL or siPTTG1."
| 1 5
| 4

reach
"The combination of dabrafenib and trametinib suppressed cell growth in the resistant lines."

reach
"In a preclinical study, dabrafenib plus trametinib synergistically inhibited cell growth in a BRAF V600E-mutant lung carcinoma cell line (MV522; data on file)."

reach
"The durability of these responses was determined by 4-week colony formation assays in which dabrafenib completely suppressed the WM1366 cell growth, but vemurafenib did not."

reach
"Furthermore, treatment of dabrafenib resistant melanoma cells with BRAF inhibitor in combination with phosphoinositide 3-kinase/mTOR inhibitor GSK2126458 inhibited cell growth (Greger et al., 2012)."
Dabrafenib activates cell growth.
| 1 1
| 1 1

reach
"Both SK-MEL-28VR1 and 501-mel cells showed a reduction in cell growth when simultaneously treated with MTX and dabrafenib compared to MTX or dabrafenib single treatments or vehicle only treatments."

medscan
"Combination of dabrafenib with AKTi enhances cell growth inhibition in dabrafenib sensitive (A) and resistant cell lines (B) but not in very sensitive cell lines (C)."
| 6
Dabrafenib inhibits Neoplasms.
| 4

medscan
"In addition, dabrafenib and trametinib treatment of CD73+BRAFV600E-mutant melanomas caused profound CD73 downregulation in tumor cells."

medscan
"Dabrafenib selectively inhibits cell viability in B-RafV600E mutant cancer cells."

medscan
"Combined treatment with dabrafenib and trametinib was able to overcome resistance in preclinical models and use in patients with B-RAF mutated tumors resulted in improved progression free survival [ ]."

medscan
"BRAF pathway plays an important role in tumorigenesis in non-small cell lung cancer, BRAF inhibitors, vemurafenib and dabrafenib have shown only modest efficacy in BRAF-V600E mutant cancers [ , ]. 46999999="V600E"}"
Dabrafenib activates Neoplasms.
| 2

medscan
"Monotherapy with vemurafenib, dabrafenib, and encorafenib induces neoplasia, most often cutaneous squamous cell carcinoma , at rates of approximately 22%, 6%, and 3.7%, respectively [ , - ], averaged across multiple phase I-III trials conducted in heterogeneous patient populations."

medscan
"Recent clinical evidence suggest that Vemurafenib and GSK2118436 therapy enhances CD8+ T cell infiltration of the tumor mass, which correlates with the degree of tumor shrinkage ( )."
Y-27632 affects RHOA
| 4 2
Y-27632 inhibits RHOA.
| 4
Y-27632 inhibits RHOA. 4 / 4
| 4

medscan
"We found that blockade of RhoA with C3 exoenzyme or inhibition of RhoA kinase by the specific inhibitor Y-27632 enhanced phorbol ester-stimulated alpha(4)beta(1)-dependent adhesion of Jurkat cells at 30 min."

medscan
"Furthermore, Y-27632, an inhibitor of ROCK2, attenuated the Angiotensin II-induced contraction of human airway smooth muscle cells by blocking the RhoA/ROCK2 signaling pathway which is involved in this contraction, and thus may be a major regulator involved in the basal maintenance of contractility in human airway smooth muscle cells."

medscan
"Suppression of RhoA and Rho-kinase activities by anti-RhoA immunoglobulin G electroporation and Y-27632, respectively prevented morphologic changes and restored plasma membrane localization of occludin."

medscan
"RhoA siRNA and RhoA activation inhibitor, Y-27632, markedly reduce the angiotensin II effect."
Y-27632 activates RHOA.
| 2
Y-27632 activates RHOA. 2 / 2
| 2

reach
"We also noted that feeder cells and altered molecular pathways activate telomerase (Fu et al. 2003; Liu et al. 2008; Liu et al. 2009; Klingelhutz and Roman 2012; Liu et al. 2012), and a Rho-Kinase inhibitor, Y-27632, disrupts the actin cytoskeleton and inactivate Rho (Chapman et al. 2010; Liu et al. 2012)."
| PMC

reach
"Furthermore, Y-27632, an inhibitor of ROCK2, attenuated the Ang II-induced contraction of HASMCs by blocking the RhoA/ROCK2 signaling pathway which is involved in this contraction, and thus may be a major regulator involved in the basal maintenance of contractility in HASMCs."
3 2 | 1
Sotrastaurin inhibits PRKCB.
3 1 | 1
3 | 1

tas
No evidence text available

reach
"AEB071 blocks the catalytic activity of PKCalpha, PKCbeta and PKCtheta isoforms at a low picomolar concentration range, as well as PKCdelta, PKCepsilon and PKCetaat higher, nanomolar, concentrations [XREF_BIBR]."

tas
No evidence text available

tas
No evidence text available
1 |

ctd
No evidence text available
Sotrastaurin phosphorylates PRKCB.
1 |
Sotrastaurin phosphorylates PRKCB. 1 / 1
1 |

ctd
No evidence text available
Dabrafenib affects MAP2K1
| 6
Dabrafenib inhibits MAP2K1.
| 2
| 2

reach
"Finally, dabrafenib and trametinib are small molecule inhibitors of BRAF and MEK1 and MEK2, respectively."

reach
"The combination of dabrafenib and rigosertib appeared to suppress the positive regulation and promote the negative regulation of MEK1."
Dabrafenib phosphorylates MAP2K1.
| 2
Dabrafenib leads to the phosphorylation of MAP2K1 on T286. 1 / 1
| 1

reach
"The combination of dabrafenib and rigosertib suppressed the positively regulated phosphorylation of MEK1 at Ser217/221 and ERK1/2 at Thr202 and Tyr204, promoted the negatively regulated phosphorylation of MEK1 at Thr286, and maintained the negatively regulated phosphorylation of MEK1 at Thr292 and Thr386."
Dabrafenib leads to the phosphorylation of MAP2K1. 1 / 1
| 1

reach
"The combination of dabrafenib and rigosertib suppressed the positively regulated phosphorylation of MEK1 at Ser217/221 and ERK1/2 at Thr202 and Tyr204, promoted the negatively regulated phosphorylation of MEK1 at Thr286, and maintained the negatively regulated phosphorylation of MEK1 at Thr292 and Thr386."
Dabrafenib dephosphorylates MAP2K1.
| 1
Dabrafenib leads to the dephosphorylation of MAP2K1 on T286. 1 / 1
| 1

reach
"The combination of dabrafenib and rigosertib suppressed the positively regulated phosphorylation of MEK1 at Ser217/221 and ERK1/2 at Thr202 and Tyr204, promoted the negatively regulated phosphorylation of MEK1 at Thr286, and maintained the negatively regulated phosphorylation of MEK1 at Thr292 and Thr386."
Dabrafenib activates MAP2K1.
| 1
| 1

reach
"The MEK1 T55delinsRT mutation can be targeted by combination therapy of dabrafenib and trametinib (Fig XREF_FIG, Supplementary Figs S3 and S4)."
3 | 2
Sotrastaurin inhibits PRKCD.
3 | 1
3 | 1

tas
No evidence text available

tas
No evidence text available

reach
"AEB071 blocks the catalytic activity of PKCalpha, PKCbeta and PKCtheta isoforms at a low picomolar concentration range, as well as PKCdelta, PKCepsilon and PKCetaat higher, nanomolar, concentrations [XREF_BIBR]."

tas
No evidence text available
Sotrastaurin activates PRKCD.
| 1
| 1

reach
"Sotrastaurin attenuates the stemness of gastric cancer cells by targeting PKCdelta."
Dabrafenib affects hPXR
| 2 1 2
Dabrafenib activates hPXR.
| 1 1 2
Dabrafenib activates hPXR. 4 / 4
| 1 1 2

reach
"Using different reporter cellular assays, we demonstrate that dabrafenib can activate hPXR as efficiently as its reference agonist SR12813, whereas it does not activate mouse or zebrafish PXR nor hCAR."

eidos
"Using different reporter cellular assays , we demonstrate that dabrafenib can activate hPXR as efficiently as its reference agonist SR12813 , whereas it does not activate mouse or zebrafish PXR nor hCAR ."

reach
"In that context, the potential of the anticancer BRAF inhibitor dabrafenib suspected to activate hPXR and the human constitutive androstane receptor (hCAR) has not been thoroughly investigated yet."

isi
"Using different reporter cellular assays, we demonstrate that dabrafenib can activate hPXR as efficiently as its reference agonist SR12813, whereas it does not activate mouse or zebrafish PXR nor hCAR."
Dabrafenib binds hPXR.
| 1
Dabrafenib binds hPXR. 1 / 1
| 1

isi
"We also showed that dabrafenib binds to recombinant hPXR, induces the expression of hPXR responsive genes in colon LS174T-hPXR cancer cells and human hepatocytes and finally increases the proliferation in LS174T-hPXR cells."
| 5
Dabrafenib activates cell death.
| 4

reach
"In addition, z-VAD increased cell death induced by acetaminophen, which was prevented by dabrafenib partly (XREF_SUPPLEMENTARY); dabrafenib but not vemurafenib decreased the acetaminophen induced loss of the cell viability (XREF_SUPPLEMENTARY)."

reach
"We observed that the combination of vemurafenib or dabrafenib with TH1579 significantly reduced cell proliferation and induced cell death (p < 0.01) in A375, A375VR4, and ESTDAB049 cell lines compared with either treatment alone."

reach
"ER stress response plays a protective role and provides resistance to dabrafenib mediated cell death in melanoma."

reach
"Additional compounds and antibodies for targeted, immuno- as well as combination therapy have been and are currently being developed such as the BRAF V600mut inhibitor dabrafenib [XREF_BIBR], mitogen activated protein kinase kinase (MEK) inhibitors trametinib [XREF_BIBR] and cobimetinib [XREF_BIBR], the anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody ipilimumab [XREF_BIBR] as well as anti-programmed cell death protein 1 (PD-1) antibodies pembrolizumab [XREF_BIBR] and nivolumab [XREF_BIBR]."
| 1

reach
"We observed that pretreatment of cells with Nec1s, as well as an RIPK3 inhibitor dabrafenib, prevented crystalline particle induced cell death."
| 1 4
Dabrafenib activates cell cycle.
| 4

reach
"FACS cell cycle analysis revealed that 25 nM dabrafenib induced G0/G1 cell cycle arrest of the A375 cells, but not the A375R cells."

reach
"Next, we examined the cell cycle profiles of BRAFi resistant MM cells treated with MTX + dabrafenib drug combinations."

reach
"Vemurafenib, encorafenib and dabrafenib induce cell cycle arrest and apoptosis in BRAF melanoma cell lines; however, a residual population of tumor cells survive."

reach
"Like vemurafenib, dabrafenib decreases phosphorylated ERK and causes cell cycle arrest."
| 1

eidos
"Vemurafenib , encorafenib and dabrafenib induce cell cycle arrest and apoptosis in BRAF melanoma cell lines ; however , a residual population of tumor cells survive ."
| 4

reach
"TAS-116 also enhanced dabrafenib induced MM cytotoxicity associated with mitochondrial damage induced apoptosis, even in the BRAF mutated U266 MM cell line."

reach
"Taken together, these results indicate that TAS-116 enhances dabrafenib induced MM cytotoxicity and apoptosis, even in the BRAF mutated U266 MM cells."

reach
"Because HSP90 inhibitors block multiple pathways crucial to MM survival [XREF_BIBR, XREF_BIBR, XREF_BIBR], the combination of TAS-116 and dabrafenib enhances the anti-MM effect in RAS mutated and wild-type BRAF MM cells via a mechanism other than ERK pathway inhibition."

reach
"Next, we examined the cell cycle profiles of BRAFi resistant MM cells treated with MTX + dabrafenib drug combinations."

reach
"TAS-116 or dabrafenib significantly inhibited the viability of U266 MM cells in a dose- and time dependent manner (XREF_FIG)."

reach
"In contrast, BCR pathway inhibitors such as ibrutinib, idelalisib, duvelisib, MK2206, AEB-071, dasatinib or alkylating agent such as bend-amustine did not result in synergy [XREF_BIBR, XREF_BIBR]."

reach
"Additionally, AEB071 attenuates BCR mediated survival pathways, inhibits CpG induced survival and proliferation of CLL cells in vitro, and effectively blocks microenvironment mediated survival signaling pathways in primary CLL cells."

reach
"Sotrastaurin selectively inhibited the growth of CD79 mutant BCR subtypes of ABC-DLBCL in vitro and in vivo whereas the presence of CARD11 mutations resulted in resistance to the inhibitor [XREF_BIBR]."

reach
"Mantle cell lymphoma is an aggressive malignancy supported by aberrant B cell receptor (BCR) signaling, which is targeted by inhibitors ibrutinib and sotrastaurin."

reach
"Ibrutinib and AEB071 target BCR signaling upstream of CARD11, which participates in NF-kB activation as part of the CARD11/BCL10/MALT1 (CBM) complex."
| 5
Sotrastaurin dephosphorylates RASGRP3.
| 3
Sotrastaurin leads to the dephosphorylation of RASGRP3 on T133. 2 / 2
| 2

reach
"At a concentration of 1 muM AEB071 was able to completely abrogate T133 phosphorylation of RasGRP3, consistent with prior studies showing complete extinction of PKC activity at this concentration."

reach
"At a concentration of 1 muM AEB071 was able to completely abrogate T133 phosphorylation of RasGRP3, consistent with prior studies showing complete extinction of PKC activity at this concentration (Chen et al., 2014)."
Sotrastaurin leads to the dephosphorylation of RASGRP3. 1 / 1
| 1

reach
"This time course contrasts with the suppression of RasGRP3 phosphorylation by AEB071, which was detectable already at 2 hr and peaked at 10 hr."
Sotrastaurin inhibits RASGRP3.
| 2

reach
"The PKC inhibitors AEB071 and AHT956 also both decreased RasGRP3 mRNA, also with no effect on SOS1 mRNAs (XREF_SUPPLEMENTARY)."

reach
"The PKC inhibitors AEB071 and AHT956 also both decreased RasGRP3 mRNA, also with no effect on SOS1 mRNAs."
Dabrafenib affects AKT
| 5
Dabrafenib activates AKT.
| 3
| 2

reach
"Intraperitoneal daily delivery of BRAF V600E inhibitor dabrafenib only transiently suppressed MAPK signaling, and rather increased Akt signaling and failed to extend survival for mice with intracranial 2341 luc tumor."

reach
"Lapatinib blocked the superactivated HER2 and HER3, AKT and pERK1/2 induced by dabrafenib."
Dabrafenib activates phosphorylated AKT. 1 / 1
| 1

reach
"Moreover, TAS-116 markedly inhibited p-C-Raf or p-Akt, which were paradoxically activated by dabrafenib in the U266 MM cell line."
Dabrafenib inhibits AKT.
| 1
| 1

reach
"Moreover, we found that sorafenib reversed dabrafenib inhibition of AKT in HT-29cells, and phosphatidylinositol-3-kinase (PI3K) inhibitor GDC0941 significantly restored this antagonistic effect when combined with dabrafenib and sorafenib, indicating that AKT is critically involved in this antagonism."
Dabrafenib dephosphorylates AKT.
| 1
Dabrafenib leads to the dephosphorylation of AKT. 1 / 1
| 1

reach
"LY-294002 abolished the basal and induced phosphorylation of AKT, and dabrafenib slightly reduced the FSS induced phosphorylation of AKT."
Sotrastaurin affects phosphorylation
| 4
Sotrastaurin inhibits phosphorylation. 4 / 4
| 4

sparser
"To determine if PKC activation was related to ERK phosphorylation, we treated cells with the PKC inhibitor AEB071 that inhibits PKC phosphorylation induced by PMA (4β-phorbol 12-myristate 13-acetate), a specific activator of PKC (Figure xref )."

sparser
"This is consistent with previous reports indicating that AEB071 inhibits ERK1/2 phosphorylation in GNAQ mutant cell lines ( xref )."

sparser
"AEB071 inhibited Erk1/2 phosphorylation in GNAQ mutated but not GNAQ wild type UM cells, and had minimal impact on Akt phophorylation."

sparser
"However, AEB071 only significantly inhibited Erk1/2 phosphorylation in GNAQ mutant cells while it had minimal effect on Akt phosphorylation in both GNAQ wild type and mutated cells ( xref )."
3 | 1
3 | 1

tas
No evidence text available

tas
No evidence text available

reach
"AEB071 blocks the catalytic activity of PKCalpha, PKCbeta and PKCtheta isoforms at a low picomolar concentration range, as well as PKCdelta, PKCepsilon and PKCetaat higher, nanomolar, concentrations [XREF_BIBR]."

tas
No evidence text available
3 | 1
3 | 1

reach
"AEB071 blocks the catalytic activity of PKCalpha, PKCbeta and PKCtheta isoforms at a low picomolar concentration range, as well as PKCdelta, PKCepsilon and PKCetaat higher, nanomolar, concentrations [XREF_BIBR]."

tas
No evidence text available

tas
No evidence text available

tas
No evidence text available
Dabrafenib affects mtnN
| 4
| 4

reach
"Copy number changes in CDKN2A, CCND1, and mutation and copy number changes in PTEN correlated with the duration of PFS in patients treated with dabrafenib."

reach
"The combination of dabrafenib with trametinib significantly increased PFS over dabrafenib alone in a phase II study [XREF_BIBR]."

reach
"Median PFS was significantly improved at 9.4 months for the patients treated with 150mg dabrafenib twice daily and 2mg trametinib daily, as compared with 5.8 months for the patients treated with dabrafenib alone (HR for progression or death, 0.39; 95% CI, 0.25-0.62; P < 0.001)."

reach
"Increased cyclin D expression mediates inherent resistance to mutant BRAF inhibition [XREF_BIBR], and copy number changes in CDKN2A, CCND1 correlated with the shortened duration of PFS in patients treated with dabrafenib [XREF_BIBR]."
Dabrafenib affects PTEN
| 4
| 4

reach
"In a study by Nathanson et al. [XREF_BIBR], patients with wild-type PTEN treated with BRAF inhibitor dabrafenib had longer PFS compared with patients with at least one mutated allele of PTEN (32.1 vs 18.3 weeks; p = 0.066), and a modest association between low expression of PTEN and lower response was observed in the phase 2 study of vemurafenib as well [XREF_BIBR]."

reach
"Furthermore, she showed data on PTEN as a marker of progression-free survival among patients treated with dabrafenib."

reach
"Copy number changes in CDKN2A, CCND1, and mutation and copy number changes in PTEN correlated with the duration of PFS in patients treated with dabrafenib."

reach
"On the other hand, tissue expression of PTEN was associated with shorter PFS in patients treated with dabrafenib [XREF_BIBR]."
| 4
| 4

medscan
"To determine whether brivanib inhibits growth factor-induced proliferation of hepatic stellate cells, we examined the effect of increasing concentrations of brivanib on LX-2 hepatic stellate cell proliferation under control conditions or after stimulation with concentrations of platelet-derived growth factor, VEGF, and FGF2 shown to induce LX-2 proliferation."

medscan
"Our findings demonstrate that brivanib reduces liver fibrosis in three different animal models, and inhibits growth factor-induced stellate cell proliferation and activation."

medscan
"Our findings that brivanib inhibits not only VEGF- and fibroblast growth factor-mediated proliferation of hepatic stellate cells, but also inhibits platelet-derived growth factor-induced proliferation, together with our other findings that brivanib abrogates phosphorylation of the platelet-derived growth factorβ receptor, suggest the need to further characterize the modulation of platelet-derived growth factor signaling by brivanib."

medscan
"In vitro, brivanib decreased proliferation of hepatic stellate cells induced by platelet-derived growth factor , VEGF, and FGF."
A-674563 affects PRKACA
3 1 |
3 1 |

drugbank
No evidence text available

tas
No evidence text available

tas
No evidence text available

tas
No evidence text available
| 4
| 3

reach
"Sotrastaurin exposure does not seem to be altered by everolimus, but sotrastaurin increases everolimus exposure by 20%."

reach
"Sotrastaurin increased everolimus C (max) from 15 +/- 6 to 16 +/- 6 ng/ml yielding a ratio of 1.15 (0.99 - 1.33) and increased everolimus total AUC from 114 +/- 50 to 137 +/- 56 ng * h/ml yielding a ratio of 1.20 (1.05 - 1.37)."

reach
"Everolimus AUC was increased 20% by sotrastaurin."
Sotrastaurin increases the amount of everolimus.
| 1
Sotrastaurin increases the amount of everolimus. 1 / 1
| 1

reach
"The possibility that a higher dose of sotrastaurin than used in this study might further increase everolimus blood levels can not be excluded."
| 4
| 3

reach
"This is important since higher concentrations of AEB071 are known to cause cell cycle perturbations and apoptosis in certain cell types."

reach
"The protein kinase C (PKC) inhibitor sotrastaurin induced cell cycle arrest and/or cell death in ABC DLBCL cell lines and in a mouse xenograft model [XREF_BIBR]."

reach
"Furthermore, we demonstrated that the PKC inhibitor sotrastaurin induced cell apoptosis and cell cycle arrest in DLBCL cells potentially through regulating the expression of MCT-1."
| 1

reach
"Inhibition of PKC alone such as by AEB071 or sotrastaurin induced cell cycle G1 phase arrest and suppressed PKC and ERK1/2 signaling."

reach
"Momelotinib significantly suppressed the development of CSC like markers associated with paclitaxel treatment in ovarian cancer cell lines."

reach
"However, the discontinuation of paclitaxel and momelotinib treatment no longer suppressed JAK2 and STAT3 activation and CSC like development, thus allowing the resumption of tumor growth and dissemination."

reach
"The addition of daily momelotinib to weekly paclitaxel treatment significantly inhibited the JAK2 and STAT3 activation and CSC like phenotypes in mice tumors."
Momelotinib decreases the amount of Neoplastic Stem Cells.
| 1
Momelotinib decreases the amount of Neoplastic Stem Cells. 1 / 1
| 1

reach
"Phase 1 : Daily momelotinib administration in conjunction with weekly paclitaxel significantly reduced in vivo expression of CSC markers and associated tumorigenicity of HEY cells in mice."
Momelotinib affects JAK
| 4
Momelotinib inhibits JAK.
| 3
| 3

reach
"Furthermore, IGF1R inhibitors such as linsitinib (OSI-906), MEK inhibitors such as selumetinib (AZD6244) or trametinib (GSK1120212) and JAK and TBK1 inhibitors such as momelotinib (CYT387) each have a unique side effect profile and sets of nonoverlapping toxicities."

reach
"JAK family inhibitors like TG101209 or momelotinib (formerly Cytopia387) have been shown to partially normalize cytokine concentrations in mice with JAK2 V617F -induced MPN."

reach
"Conversely, JAK and STAT signaling was selectively activated in CBL iPSCs and abrogated by the JAKi momelotinib and ruxolitinib."
Momelotinib activates JAK.
| 1
| 1

reach
"Momelotinib therapy targets the JAK and STAT family, a key prosurvival pathway that controls apoptotic signals in hematological malignancies [XREF_BIBR]."
Dabrafenib affects RAF
| 4
Dabrafenib inhibits RAF.
| 3
| 3

reach
"In case of light induced BRAF, vemurafenib enhanced and dabrafenib inhibited the RAF kinase cascade activity."

reach
"Higher concentrations of dabrafenib inhibited RAF signaling without further affecting the level of CRAF proteins."

reach
"Approved Raf kinase inhibitors, such as dabrafenib and vemurafenib, are ineffective inhibitors of c-Raf and so clinical testing of this hypothesis will have to await the emergence of true c-Raf inhibitor drugs."
Dabrafenib activates RAF.
| 1
| 1

reach
"In contrast, in CRAF-CRY2 expressing cells dabrafenib induced paradoxical activation of RAF signaling in dark which was even more pronounced upon light exposure."
A-674563 affects CDK2
3 | 1
A-674563 inhibits CDK2.
3 |
3 |

tas
No evidence text available

tas
No evidence text available

tas
No evidence text available
A-674563 activates CDK2.
| 1
A-674563 activates CDK2. 1 / 1
| 1

reach
"A-674563, a putative AKT1 inhibitor that also suppresses CDK2 activity, inhibits human NSCLC cell growth more effectively than the pan-AKT inhibitor, MK-2206."
A-674563 affects AKT
| 4
A-674563 inhibits AKT.
| 2
A-674563 inhibits AKT. 2 / 2
| 2

reach
"For the molecular study, we showed that A-674563 blocked Akt activation in U937 cells and human AML progenitor cells."

reach
"Further, A-674563 treatment blocked Akt and its downstream S6 Kinase 1 (S6K1) activation in A375 melanoma cells."
A-674563 increases the amount of AKT.
| 2
A-674563 increases the amount of phosphorylated AKT. 2 / 2
| 2

reach
"p-AKT levels are decreased by MK-2206 and increased by A-674563."

reach
"A-674563 was found to increase the expression of p-AKT (Ser473) and p-AKT (Thr308) in both cell lines."
Sotrastaurin affects PKC isoforms
| 4
Sotrastaurin inhibits PKC isoforms.
| 2
Sotrastaurin inhibits PKC isoforms. 2 / 2
| 2

reach
"To better understand differential responses of UM cells to AEB071 based on GNAQ mutational status, we examined inhibition of PKC isoforms by AEB071 in UM cells."

reach
"The inhibition of PKC isoforms by AEB071 prevents the production of several cytokines."
Sotrastaurin dephosphorylates PKC isoforms.
| 1
Sotrastaurin leads to the dephosphorylation of PKC isoforms. 1 / 1
| 1

reach
"AEB071 inhibits expression and phosphorylation of PKC isoforms in UM cells."
Sotrastaurin decreases the amount of PKC isoforms.
| 1
Sotrastaurin decreases the amount of PKC isoforms. 1 / 1
| 1

reach
"AEB071 inhibits expression and phosphorylation of PKC isoforms in UM cells."
Dabrafenib affects TNF
1 | 3
Dabrafenib inhibits TNF.
| 2
| 2

reach
"Dabrafenib blocked lipopolysaccharides induced activation of TNF-alpha in bone marrow derived macrophages, suggesting that Dabrafenib may attenuate TNF-alpha-induced necroptotic pathway after ischemic brain injury."

reach
"In human vascular endothelial cells, Dabrafenib markedly attenuates the activation of TNF-alpha (Jung et al., 2016)."
Dabrafenib increases the amount of TNF.
1 |
Dabrafenib increases the amount of TNF. 1 / 1
1 |

ctd
No evidence text available
Dabrafenib decreases the amount of TNF.
| 1
Dabrafenib decreases the amount of TNF. 1 / 1
| 1

reach
"Although Dabrafenib treatment did not result in a significant reduction in Iba1 + microglia recruitment to the site of injury (XREF_FIG), Dabrafenib treatment attenuated up-regulation of TNF-alpha mRNA levels one day after photothrombosis (XREF_FIG, Dabrafenib effect : F = 5.479, P = 0.037; time effect : F = 15.412, P = 0.002)."

sparser
"Sotrastaurin inhibited the NF-κB dependent cytokine production in the T cell subsets by 88.5%, 85.7%; and 88.0% respectively (p<0.01 compared to no drug; xref )."

reach
"Sotrastaurin inhibited the NF-kappaB dependent cytokine production in the T cell subsets by 88.5%, 85.7%; and 88.0% respectively (p < 0.01 compared to no drug; XREF_FIG)."

reach
"Sotrastaurin prevented TCR and CD28 induced T-cell activation and pro inflammatory cytokine production, but preserved a stable Treg phenotype as evidenced by maintenance of suppressive capacity, high Foxp3 and CD25 expression, and lack of IL-17A and IFNgamma production."
Sotrastaurin affects RPS6
| 1 2
| 1 2

sparser
"AEB071 inhibited p-MARCKS, a PKC substrate, and pS6 in all the cell lines, independently of the mutational status."

reach
"AEB071 inhibited p-MARCKS, a PKC substrate, and pS6 in all the cell lines, independently of the mutational status."

reach
"In these cells AEB071 inhibited p-MARCKS and p-S6 but induced activation of p-AKT over time, which was inhibited by BYL719 in the combination therapy."
3 |
3 |

tas
No evidence text available

tas
No evidence text available

tas
No evidence text available
Sotrastaurin affects NFAT
| 1 2
| 1 2

reach
"Furthermore, the PKC-theta inhibitor AEB071 inhibits NFkappaB and NFAT but not AP1 activity XREF_BIBR."

reach
"However, the finding that the combined deletion of PKCtheta and PKCalpha primarily affects NFAT activation is inconsistent with findings that AEB071 does not inhibit NFAT activation."

sparser
"Furthermore, the PKC-θ inhibitor AEB071 inhibits NFκB and NFAT but not AP1 activity xref ."
2 | 1
2 | 1

reach
"Similarly, AEB071 decreased GSK3beta Ser9 phsophorylation in all UM cell lines studied here (XREF_SUPPLEMENTARY)."

tas
No evidence text available

tas
No evidence text available
Sotrastaurin affects ABC-DLBCL
| 3
Sotrastaurin inhibits ABC-DLBCL. 3 / 3
| 3

reach
"Preclinical studies demonstrated that sotrastaurin (AEB071) and enzastaurin, two adenosine triphosphate-competitive selective inhibitors of PKCbeta, induce apoptosis and inhibit the proliferation of BCR-subtypes of ABC-DLBCL in vitro and in vivo [XREF_BIBR, XREF_BIBR]."

reach
"Preclinical studies demonstrated that sotrastaurin (AEB071) and enzastaurin, two adenosine triphosphate-competitive selective inhibitors of PKCbeta, induce apoptosis and inhibit the proliferation of BCR-subtypes of ABC-DLBCL in vitro and in vivo [XREF_BIBR, XREF_BIBR]."

reach
"Sotrastaurin selectively inhibited the growth of CD79 mutant BCR subtypes of ABC-DLBCL in vitro and in vivo whereas the presence of CARD11 mutations resulted in resistance to the inhibitor [XREF_BIBR]."

reach
"Furthermore, apoptosis induced by momelotinib treatment was suppressed by LKB1 re-expression in KL A549 cells."

reach
"Indeed, single-agent momelotinib treatment induced apoptosis in KL and KLP but not in KP cells."

reach
"In the sensitive cell lines (WSU-NHL, RL, Karpas-422, Jeko-1, and L540) the citarinostat+ momelotinib combination induced apoptosis mediated by the intrinsic (mitochondrial) apoptotic pathway."
Dabrafenib affects TLE5
| 3
| 3

reach
"The most common AEs noted in patients treated with dabrafenib were hyperkeratosis (37%), headache (32%), pyrexia (28%), arthralgia (27%) and skin papillomas (24%)."

reach
"XREF_BIBR The successful use of dabrafenib in case of vemurafenib induced severe AEs have been reported."

reach
"XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR The AEs are also tolerable for those patients treated with dabrafenib when compared with approved therapies for second- and third-line NSCLC."
Dabrafenib affects NEK9
| 1 2
| 1 2

reach
"Dabrafenib, a medication for the treatment of BRAF-associated cancers, is predicted to inhibit NEK9, an interactor of NSP9."

eidos
"Dabrafenib , a medication for the treatment of BRAF-associated cancers , is predicted to inhibit NEK9 , an interactor of NSP9 ."

reach
"In cell based studies of NRAS- and KRAS-mutant cancer cells, dabrafenib inhibited the NEK9 target CHK1, whereas vemurafenib did not."
Dabrafenib affects MCL1
| 3
Dabrafenib increases the amount of MCL1. 3 / 3
| 3

reach
"As observed earlier, dabrafenib at a concentration of 10 nM significantly induced the expression of Mcl-1 in A375, SK-MEL-28, SK-MEL-5 and WM-239 cells."

reach
"Similar to vemurafenib, we observed that dabrafenib treatment also induced massive Mcl-1 expression at all the three concentrations."

reach
"Dabrafenib induces Mcl-1 expression in melanoma cells."
Dabrafenib affects CYP2C9
| 1 2
| 1 2

reach
"Because dabrafenib induces CYP3A4 and CYP2C9 it decreased the systemic exposures of the CYP3A4 substrate midazolam, the CYP2C9 substrate S-warfarin, and the CYP3A4/CYP1A2 substrate R-warfarin.XL281 (BMS-908662) is a highly selective inhibitor of B-RAF and C-RAF, but not A-RAF."
| PMC

reach
"Because dabrafenib induces CYP3A4 and CYP2C9 it decreased the systemic exposures of the CYP3A4 substrate midazolam, the CYP2C9 substrate S-warfarin, and the CYP3A4/CYP1A2 substrate R-warfarin."
| PMC

eidos
"Because dabrafenib induces CYP3A4 and CYP2C9 it decreased the systemic exposures of the CYP3A4 substrate midazolam , the CYP2C9 substrate S-warfarin , and the CYP3A4 / CYP1A2 substrate R-warfarin ."
| PMC
Brivanib affects Liver Cirrhosis
| 3
Brivanib inhibits Liver Cirrhosis. 3 / 3
| 3

medscan
"Our findings demonstrate that brivanib reduces liver fibrosis in three different animal models, and inhibits growth factor-induced stellate cell proliferation and activation."

medscan
"In this study we have shown that brivanib reduces liver fibrosis in three different animal models through effects on platelet-derived growth factor, VEGF and fibroblast growth factor signaling."

medscan
"Our results suggest that brivanib inhibits liver fibrosis through effects on multiple signaling pathways."
Y-39983 affects RHOA
| 3
Y-39983 inhibits RHOA. 3 / 3
| 3

reach
"Similarly, different Rho kinase inhibitors including HA1007 (fasudil), Y-39983 (SJN-1656), ripasudil (K-115) and Y-27632 were found to exhibit neuroprotection by promoting axonal outgrowth and RGC survival in different animal models (Bermel et al., 2009; Hirata et al., 2008; Kitaoka et al., 2004; Sagawa et al., 2007; Sugiyama et al., 2011; Van de Velde et al., 2015; Yamamoto et al., 2014; Yu et al., 2015, 2016)."

reach
"Similarly, different Rho kinase inhibitors including HA1007 (fasudil), Y-39983 (SJN-1656), ripasudil (K-115) and Y-27632 were found to exhibit neuroprotection by promoting axonal outgrowth and RGC survival in different animal models."

reach
"More specific Rho kinase inhibitors, such as Y-27632, Y-39983, HA-1077, H-1152 and INS117548, increase outflow facility and/or decrease IOP in living rabbits and monkeys and/or enucleated animal eyes, similar to H-7 [XREF_BIBR - XREF_BIBR, XREF_BIBR - XREF_BIBR]."
Y-27632 affects PKN2
3 |
Y-27632 inhibits PKN2. 3 / 3
3 |

tas
No evidence text available

tas
No evidence text available

tas
No evidence text available
Y-27632 affects Carcinoma, Renal Cell
| 3
Y-27632 inhibits Carcinoma, Renal Cell. 3 / 3
| 3

medscan
"Second, we have shown that the ROCK inhibitor Y-27632 suppresses Clear Cell Renal Cell Carcinoma tumor growth in vivo."

medscan
"Finally, Y-27632 treatment inhibited growth of subcutaneous 786-OT1 Clear cell renal cell carcinoma tumors in mice."

medscan
"Together these results indicate that Y-27632 inhibits ROCK in Clear Cell Renal Cell Carcinoma and selectively targets Von Hippel Lindau-deficient Clear Cell Renal Cell Carcinoma while sparing Von Hippel Lindau-reconstituted Clear Cell Renal Cell Carcinoma in multiple genetic backgrounds."
KW2449 affects FLT3
3 |
KW2449 inhibits FLT3. 3 / 3
3 |

tas
No evidence text available

tas
No evidence text available
| DOI

tas
No evidence text available
KW2449 affects DNA Damage
| 3
| 3

reach
"These findings argue that while ROS generation plays a significant functional role in HDACI and KW2449 mediated DNA damage and apoptosis in Bcr and Abl + leukemia cells, additional factors may be involved in lethality."

reach
"The finding that HDACIs potentiated DNA damage induced by KW2449 (or other Bcr and Abl kinase inhibitors) reflected by increased expression of lambdaH2A.X, a marker for double-strand DNA breaks, has also not been previously described."

reach
"In view of evidence that Bcr and Abl kinase inhibitors can disrupt DNA repair mechanisms in Bcr and Abl + cells [XREF_BIBR], the effects of HDACIs on KW2449 induced DNA damage was examined."
KW2449 affects ABL1
1 | 2
KW2449 inhibits ABL1. 3 / 3
1 | 2

reach
"Although the multi-kinase inhibitor KW2449, which also inhibits Bcr and Abl and aurora kinases, has primarily been developed as a FLT3 inhibitor in AML [XREF_BIBR], preclinical studies demonstrate that it effectively kills Bcr and Abl + leukemias, including Ph + ALL, bearing gatekeeper mutations [XREF_BIBR]."

tas
No evidence text available

reach
"In IM resistant BV173 and E255K and Adult and T315I cells, coadministration of KW2449 with either vorinostat or SNDX clearly inhibited Bcr and Abl activation and reduced total expression, whereas single drug treatment minimally affected Bcr and Abl levels or activation status."
A-674563 affects RPS6KB1
2 | 1
2 | 1

tas
No evidence text available

reach
"Further, A-674563 treatment blocked Akt and its downstream S6 Kinase 1 (S6K1) activation in A375 melanoma cells."

tas
No evidence text available
A-674563 affects RPS6KA3
3 |
3 |

tas
No evidence text available

tas
No evidence text available

tas
No evidence text available
A-674563 affects ROCK1
3 |
3 |

tas
No evidence text available

tas
No evidence text available

tas
No evidence text available
A-674563 affects PRKCD
3 |
3 |

tas
No evidence text available

tas
No evidence text available

tas
No evidence text available
A-674563 affects MAPK1
3 |
3 |

tas
No evidence text available

tas
No evidence text available

tas
No evidence text available
A-674563 affects GSK3B
3 |
3 |

tas
No evidence text available

tas
No evidence text available

tas
No evidence text available
Sotrastaurin affects IL2
| 3
Sotrastaurin decreases the amount of IL2.
| 2
Sotrastaurin decreases the amount of IL2. 2 / 2
| 2

reach
"Consistent with published results [XREF_BIBR], inclusion of AEB071 strongly inhibited activation determined by CD25 and CD69 expression and almost completely abolished IL-2 expression (XREF_FIG)."

reach
"Interleukin-2 messenger RNA levels were decreased by 90% +/- 9% from baseline by sotrastaurin."
Sotrastaurin inhibits IL2.
| 1
| 1

reach
"92 The PKCtheta inhibitor AEB071 decreases IL-2 and IFNgamma production by T-cells and extends rat heart and kidney allograft survive in primates."
Dabrafenib affects PTTG1
| 3
Dabrafenib decreases the amount of PTTG1.
| 2
Dabrafenib decreases the amount of PTTG1. 2 / 2
| 2

reach
"Dabrafenib abrogated PTTG1 expression and impaired invasion of the extracellular matrix (ECM) in A375 and SK-Mel28 cells."

reach
"Although further studies are required to identify the mechanisms underlying dabrafenib induced inhibition of PTTG1 expression, it is reasonable to hypothesize that drug induced impairment of the BRAF/MEK/ERK signaling cascade contributes to this molecular event."
Dabrafenib activates PTTG1.
| 1
| 1

reach
"Moreover, although dabrafenib still stimulated invasiveness in PTTG1 silenced A375R cells, ECM invasion by those cells was significantly reduced as compared to that of drug treated PTTG1 expressing cells."
Dabrafenib affects NRAS
| 3
| 2

reach
"Recent studies have identified NEK9 as a potent target of the FDA approved kinase inhibitor, dabrafenib, inhibiting growth of NRAS- and KRAS-mutant cancer cells [XREF_BIBR]."

reach
"Interestingly, dabrafenib increased NRAS and KRAS in NCI-H929 cells, and NRAS in RPMI-8226 cells."
Dabrafenib activates mutated NRAS. 1 / 1
| 1

reach
"BRAF and NRAS mutant melanoma cell lines were treated with vemurafenib, dabrafenib, trametinib, or PD0325901 and HGF or specified growth factors."
| 3
Dabrafenib activates DNA Damage.
| 2

reach
"Additionally, we identified a novel dabrafenib induced DNA damage repair delay in BRAFi resistant MM cells."

reach
"Overall, immunoblotting and cell cycle analysis revealed that MTX + dabrafenib treatments were causing G1/S arrests via ssDNA break induction by MTX coupled with dabrafenib induced DNA damage repair delay."
| 1

reach
"Dabrafenib activates the MAPK pathway and disrupts MTX induced single-strand DNA damage repair causing apoptosis in acquired resistant MM cells."
Y-27632 affects cell migration
| 3
Y-27632 inhibits cell migration.
| 2
Y-27632 inhibits cell migration. 2 / 2
| 2

medscan
"The enhancement of cancer cell migration induced by E2 was also prevented by blocking estrogen receptor with ICI 182,780, by blocking c-Src with PP2, PI3K with wortmannin or ROCK-2 with Y-27632 ( )."

medscan
"However, cell migration was abrogated with the Rho-dependent kinase inhibitor, Y-27632."
Y-27632 activates cell migration.
| 1
Y-27632 activates cell migration. 1 / 1
| 1

medscan
"However, it has been reported that a specific inhibitor of Rho-associated coiled coil-forming protein kinase, Y-27632, with a capacity of lowering intraocular pressure and increasing aqueous humor outflow in rabbits [ ], promotes human trabecular meshwork cell migration in a dose-dependent manner [ ]."
Y-27632 affects apoptotic process
| 3
Y-27632 inhibits apoptotic process.
| 2
Y-27632 inhibits apoptotic process. 2 / 2
| 2

medscan
"Administration of Y-27632 prevents apoptosis and enhances survival of human embryonic stem cells at low culture density [Watanabe et al., ], possibly through the regulation of myosin light chain phosphorylation and cell-cell interactions [Harb et al., ]."

medscan
"However, Y-27632, a specific inhibitor of the protein kinase ROCK, significantly blocked apoptosis induced by phosphorylated FKHRL1 thr-32 (P < 0.01), which was mediated by L-NMMA."
Y-27632 activates apoptotic process.
| 1
Y-27632 activates apoptotic process. 1 / 1
| 1

medscan
"Apoptosis rate was elevated with increasing concentrations of Y-27632; (4) Transwell assay showed, after a treatment with Y-27632, the number of migrated and invaded Tca8113 and CAL-27 cells in each group was statistically different (all P < 0.01); compared with controls, the number of migrated cell in groups treated with Y-27632 was decreased and less Tca8113 and CAL-27 cells in experimental groups passed through polycarbonate membrane (all P < 0.05)."
LY-2157299 affects TGFB
| 2 1
| 2

eidos
"These results are consistent with the cytostatic action of TGF-beta that negatively regulates liver regeneration , and demonstrated that galunisertib inhibited TGF-beta signaling , halted liver fibrosis progression and promoted hepatic regeneration ."

eidos
"TGF-beta may be inhibited either by galunisertib , a small molecule that inhibits AKL5 , the first element of the TGF-beta receptor 1 signaling68or by the TGF-beta receptor trap AVID200 developed by Forbious.69P-selectin may instead be inhibited by crizanlizumab , an antibody developed by Novartis , which has been shown effective to prevent pain crisis in Sickle Cell Diseases.67Phases 1-2 clinical trials with AVID200 ( NCT03094169 , open for accrual ) and Crizanlizumab ( NCT not available as yet ) in combination with ruxolitinib are in progress ."
LY-2157299 inhibits TGFB. 1 / 1
| 1

reach
"Therefore, LY-2157299 selectively inhibits TGF-beta signaling, as it has demonstrated specificity for the TGF-beta type I receptor."
| 3
Sotrastaurin phosphorylates STAT3.
| 1
Sotrastaurin leads to the phosphorylation of STAT3. 1 / 1
| 1

reach
"Moreover, idelalisib and sotrastaurin, specific inhibitors for PI3Kdelta and PKCbeta, respectively, inhibited Akt phosphorylation, NF-kappaB and STAT3 activation and Mcl-1 upregulation, and rendered cells sensitive to ATO."
Sotrastaurin inhibits STAT3.
| 1
| 1

reach
"To confirm the involvement of PI3Kdelta and PKCbeta in the resistance to ATO, we first studied whether idelalisib and sotrastaurin inhibited the activation of Akt, NF-kappaB and STAT3."
Sotrastaurin dephosphorylates STAT3.
| 1
Sotrastaurin leads to the dephosphorylation of STAT3. 1 / 1
| 1

reach
"In the presence of ATO, idelalisib and sotrastaurin significantly reduced the stroma induced phosphorylation of S473-Akt, IkappaB and STAT3."
Sotrastaurin affects MCL1
| 3
Sotrastaurin phosphorylates MCL1.
| 1
Sotrastaurin leads to the phosphorylation of MCL1. 1 / 1
| 1

reach
"Moreover, idelalisib and sotrastaurin, specific inhibitors for PI3Kdelta and PKCbeta, respectively, inhibited Akt phosphorylation, NF-kappaB and STAT3 activation and Mcl-1 upregulation, and rendered cells sensitive to ATO."
Sotrastaurin inhibits MCL1.
| 1
| 1

reach
"Further analysis of the same samples demonstrated that idelalisib and sotrastaurin significantly downregulated Mcl-1, both in untreated and ATO treated cells, while UO126 did not."
Sotrastaurin decreases the amount of MCL1.
| 1
Sotrastaurin decreases the amount of MCL1. 1 / 1
| 1

reach
"Second, idelalisib and sotrastaurin decreased Mcl-1 expression in CLL-stromal cell co-cultures treated with ATO, in correlation with a reduced CLL cell viability."
| 3
Sotrastaurin inhibits CASP3.
| 1
| 1

reach
"This was supported by our data that whereas the PKC inhibitor AEB071 inhibited G69-250-induced ERK and caspase-3 activation fully, the ROS scavenger NAC had no effect."
Sotrastaurin dephosphorylates CASP3.
| 1
Sotrastaurin leads to the dephosphorylation of CASP3. 1 / 1
| 1

reach
"Further, AEB071 (PKC inhibitor) and NAC (ROS scavenger) inhibited both ERK phosphorylation and caspase-3 activation."
Sotrastaurin activates CASP3.
| 1
| 1

reach
"In contrast, AEB071 did not increase Annexin V positive cell populations or caspase-3 cleavage in UM cells harboring wild type GNAQ (XREF_FIG)."
Sotrastaurin affects AKT
| 3
Sotrastaurin inhibits AKT.
| 1
| 1

reach
"To confirm the involvement of PI3Kdelta and PKCbeta in the resistance to ATO, we first studied whether idelalisib and sotrastaurin inhibited the activation of Akt, NF-kappaB and STAT3."
Sotrastaurin dephosphorylates AKT.
| 1
Sotrastaurin leads to the dephosphorylation of AKT. 1 / 1
| 1

reach
"Moreover, idelalisib and sotrastaurin, specific inhibitors for PI3Kdelta and PKCbeta, respectively, inhibited Akt phosphorylation, NF-kappaB and STAT3 activation and Mcl-1 upregulation, and rendered cells sensitive to ATO."
Sotrastaurin activates AKT.
| 1
Sotrastaurin activates phosphorylated AKT. 1 / 1
| 1

reach
"In these cells AEB071 inhibited p-MARCKS and p-S6 but induced activation of p-AKT over time, which was inhibited by BYL719 in the combination therapy."
Momelotinib affects STAT5
| 3
Momelotinib phosphorylates STAT5.
| 1
Momelotinib leads to the phosphorylation of STAT5 on Y701. 1 / 1
| 1

reach
"Phosphorylation of STAT1 Y701 and STAT5 Y694 was inhibited by momelotinib and ruxolitinib."
Momelotinib inhibits STAT5.
| 1
| 1

reach
"Momelotinib, an inhibitor of JAK1 and JAK2, consistently abrogated the STAT5 and LY6G6D axis in vitro, sensitizing MSS cancer cells with an intact JAK-STAT signaling, to efficiently respond to trametinib, a MEK inhibitor used in clinical setting."
Momelotinib dephosphorylates STAT5.
| 1
Momelotinib leads to the dephosphorylation of STAT5 on Y694. 1 / 1
| 1

reach
"Phosphorylation of STAT1 Y701 and STAT5 Y694 was inhibited by momelotinib and ruxolitinib."
Dabrafenib affects MLKL
| 1 2
Dabrafenib dephosphorylates MLKL.
| 2
Dabrafenib leads to the dephosphorylation of MLKL on S358. 1 / 1
| 1

reach
"Dabrafenib disrupted RIPK3 and MLKL interactions that was associated with decreased levels of MLKL phosphorylated at Ser 358 [XREF_BIBR], and prevented from induction of necroptosis in RIPK3 expressing melanoma cells [XREF_BIBR]."
Dabrafenib leads to the dephosphorylation of MLKL. 1 / 1
| 1

reach
"In addition, MLKL phosphorylation induced by these drugs was inhibited by necrostatin-1 and dabrafenib, but not necrosulfonamide, consistent with their mechanisms of action during programmed necrosis."
Dabrafenib inhibits MLKL.
| 1
| 1

medscan
"Dabrafenib decreased the RIP3-mediated Ser358 phosphorylation of mixed lineage kinase domain-like protein (MLKL) and disrupted the interaction between RIP3 and MLKL."
Y-27632 affects ACE2
| 1 2
Y-27632 inhibits ACE2.
| 1
Y-27632 inhibits ACE2. 1 / 1
| 1

eidos
"Also , Y-27632 and HA-1077 as Rho kinase inhibitors , significantly attenuated the downregulation of ACE2 in isolated rat pulmonary artery endothelial cells and restored decreased levels of ACE2 in an acute pulmonary embolism rat model [ 4,5,6 ] ."
Y-27632 increases the amount of ACE2.
| 1
Y-27632 increases the amount of ACE2. 1 / 1
| 1

reach
"Also, Y-27632 and HA-1077 as Rho kinase inhibitors, significantly attenuated the downregulation of ACE2 in isolated rat pulmonary artery endothelial cells and restored decreased levels of ACE2 in an acute pulmonary embolism rat model [4,5,6]."
Y-27632 activates ACE2.
| 1
Y-27632 activates ACE2. 1 / 1
| 1

reach
"Also, Y-27632 and HA-1077 as Rho kinase inhibitors, significantly attenuated the downregulation of ACE2 in isolated rat pulmonary artery endothelial cells and restored decreased levels of ACE2 in an acute pulmonary embolism rat model [4, 5, 6] ."
Sotrastaurin affects triple-negative breast cancer
| 2
Sotrastaurin inhibits triple-negative breast cancer. 2 / 2
| 2

medscan
"AEB071, an inhibitor of protein kinase Cθ kinase activity, also inhibits growth and invasive branching of triple-negative breast cancer cells in 3-D cultures, further supporting a role for protein kinase Cθ kinase activity in triple-negative cancer cell growth."

medscan
"These data further support the importance of protein kinase Cθ kinase activity in the oncogenic activity of triple-negative breast cancer cells, and the potential for clinical translation of protein kinase Cθ kinase inhibitors as a therapeutic option for patients with triple-negative breast cancer.Fig. 6Treatment with AEB071 inhibits protein kinase C θ activity and impairs growth of triple-negative breast cancer cells. a MDA-231-Luc-D3H2LN cells were treated with AEB071 at the indicated concentrations for 24 hours."
| 2

reach
"The protein kinase C inhibitor AEB071 (sotrastaurin) modulates migration and superoxide anion production by human neutrophils in vitro."

reach
"The protein kinase C inhibitor AEB071 (sotrastaurin) modulates migration and superoxide anion production by human neutrophils in vitro."
Sotrastaurin affects signaling
| 2
Sotrastaurin inhibits signaling. 2 / 2
| 2

sparser
"Inhibition of PKC-NF-κB signaling by AEB071 during VSV-GFP or VSV-IFN-β infection significantly inhibited the outgrowth of resistant colonies ( xref A)."

sparser
"These results indicate that AEB071 inhibits PKC signaling in vivo, but that compensatory mechanisms prevent the suppression of the MAP-kinase pathway and that the treatment is not sufficient to completely stop cell proliferation or kill cells."
Sotrastaurin affects responses
| 2
Sotrastaurin inhibits responses. 2 / 2
| 2

sparser
"Accordingly, the CD3/CD28 antibody- and alloantigen-induced T-cell proliferation responses were potently inhibited by AEB071 in the absence of nonspecific antiproliferative effects."

sparser
"Here, we show that sotrastaurin inhibited effector T-cell responses, whereas the regulatory response was enhanced."
Sotrastaurin affects psn6
| 2
| 2

sparser
"In these cells AEB071 inhibited p-MARCKS and p-S6 but induced activation of p-AKT over time, which was inhibited by BYL719 in the combination therapy."

sparser
"AEB071 inhibited p-MARCKS, a PKC substrate, and pS6 in all the cell lines, independently of the mutational status."
Sotrastaurin affects lysis
| 2
Sotrastaurin inhibits lysis. 2 / 2
| 2

sparser
"It was demonstrated that tacrolimus, rapamycin or sotrastaurin did not inhibit the lysis of autologous or allogeneic MSC by activated NK cells [ xref ], whereas these drugs are effective in suppressing T cell reactivity."

sparser
"We conclude that the immunosuppressive drugs tacrolimus, rapamycin, and sotrastaurin are not capable of inhibiting the lysis of allogeneic and autologous MSCs by activated NK cells."

reach
"In contrast, the T-cell stimulatory capacity of AEB071 treated mature monocyte derived DC (Mo-DC) is not reduced, and AEB071 administration does not prevent lipopolysaccharide (LPS)-induced Mo-DC maturation."

reach
"In contrast, the T-cell stimulatory capacity of AEB071 treated mature monocyte derived DC (Mo-DC) is not reduced, and AEB071 administration does not prevent lipopolysaccharide (LPS)-induced Mo-DC maturation."
Sotrastaurin affects activity
| 2
Sotrastaurin inhibits activity. 2 / 2
| 2

sparser
"It could be demonstrated that AEB071 significantly inhibited the cytotoxic activity of NK cells."

sparser
"AEB071 selectively inhibits NF-κB activity in GNAQ mutated UM cells."
Sotrastaurin affects PKC-mediated early T cell
| 2
Sotrastaurin inhibits PKC-mediated early T cell. 2 / 2
| 2

eidos
"168 Sotrastaurin blocks PKC-mediated early T cell activation , providing a new approach for immunosuppression distinct from CNI ."
| PMC

eidos
"Sotrastaurin blocks PKC-mediated early T cell activation , providing a new approach for immunosuppression distinct from CNI ."
| PMC
Sotrastaurin affects PIM1
2 |
2 |

tas
No evidence text available

tas
No evidence text available

reach
"Moreover, a protein kinase C inhibitor, sotrastaurin, undergoing clinical trials for the prevention of organ transplant rejection and psoriasis treatment [29], also blocked MERS-CoV infection in Huh-7 cells with an EC50 of approximately 9.7 μM with low cellular toxicity (CC50 > 50 μM)."

reach
"Moreover, a protein kinase C inhibitor, sotrastaurin, undergoing clinical trials for the prevention of organ transplant rejection and psoriasis treatment [29] , also blocked MERS-CoV infection in Huh-7 cells with an EC 50 of approximately 9.7 µM with low cellular toxicity (CC 50 > 50 µM)."
Sotrastaurin affects MAPK
| 2
| 2

reach
"Encouragingly, sotrastaurin has recently been shown to display selective cytotoxicity towards CLL cells and can inhibit their proliferation by altering the BCR-dependant survival pathways (MAPK, PI3K and NF-kappaB)."

reach
"These findings demonstrate AEB071 induced selective inhibition of the PKC and MAPK pathway in UM cells carrying GNAQ mutations."
Sotrastaurin affects JAK3
2 |
2 |

tas
No evidence text available

tas
No evidence text available
| 2

reach
"Moreover, a protein kinase C inhibitor, sotrastaurin, undergoing clinical trials for the prevention of organ transplant rejection and psoriasis treatment [29] , also blocked MERS-CoV infection in Huh-7 cells with an EC 50 of approximately 9.7 µM with low cellular toxicity (CC 50 > 50 µM)."

reach
"Moreover, a protein kinase C inhibitor, sotrastaurin, undergoing clinical trials for the prevention of organ transplant rejection and psoriasis treatment [29], also blocked MERS-CoV infection in Huh-7 cells with an EC50 of approximately 9.7 μM with low cellular toxicity (CC50 > 50 μM)."
| 2
Sotrastaurin decreases the amount of IL2RA. 2 / 2
| 2

reach
"In primary human and mouse T cells, AEB071 abrogated IL-2 secretion and CD25 expression, which are markers of early T cell activation."

reach
"The PKCtheta inhibitor AEB071 significantly suppressed SEC2 and ST-4-induced T cell proliferation, CD69 and CD25 expression, and IL-2 secretion with or without MHC II+ APCs."
| 1 1
| 1 1

sparser
"The proven potent inhibition of IL-17 by sotrastaurin makes this molecule a potential future therapeutic target in PsA [ xref ]."
| PMC

reach
"The proven potent inhibition of IL-17 by sotrastaurin makes this molecule a potential future therapeutic target in PsA [XREF_BIBR]."
| PMC
Sotrastaurin affects IFNG
| 2
| 2

reach
"This is also supported by the observation that AEB071, an inhibitor of protein kinase C-theta that preferentially halts Treg differentiation and activation, preserves graft survival and GVL but prevents IFN-gamma production and GVHD by enhancing the function of Treg."

reach
"92 The PKCtheta inhibitor AEB071 decreases IL-2 and IFNgamma production by T-cells and extends rat heart and kidney allograft survive in primates."
| 2
Sotrastaurin increases the amount of FOXP3. 2 / 2
| 2

reach
"Moreover, in both circulating and dermal psoriatic Treg, prone to rapid induction of IL-17, sotrastaurin enhanced Foxp3 expression and prevented IL-17A and IFNgamma production even when stimulated in the presence of the helper T 17 enhancing cytokines IL-1beta or IL-23."

reach
"Interestingly, sotrastaurin, a pan protein kinase C (PKC) inhibitor, has been shown to decrease effector T-cell responses and increase regulatory responses by enhancing Foxp3 expression and preventing IL-17A and IFNgamma production, even in the presence of Th17 inducing cytokines such as IL-1beta or IL-23 [XREF_BIBR]."
Sotrastaurin affects CDK2
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2 |

tas
No evidence text available

tas
No evidence text available
| 2
Sotrastaurin decreases the amount of BCL2L1. 2 / 2
| 2

reach
"Moreover, idelalisib and sotrastaurin did not significantly reduce the expression of Bcl-xL, Bcl-2 or Bfl-1, suggesting a role for Mcl-1 in the resistance to ATO induced by stroma."

reach
"AEB071 further inhibited the expression of the anti-apoptotic proteins survivin, Bcl-xL and XIAP in a dose dependent manner in Mel202, 92.1 and Omm1.3 cells (XREF_FIG)."
Momelotinib affects p65 phosphorylation
| 2
Momelotinib inhibits p65 phosphorylation. 2 / 2
| 2

eidos
"The identity of the specific member of the JAK family responsible for inhibiting p65 phosphorylation by CYT387 was sought ."

eidos
"Finally , CYT387 , but not IMD-0354 , was able to significantly diminish the p65 phosphorylation in the presence or absence of tylophorine in TGEV infected cells , as demonstrated in western analysis ( Fig. 2B-c ) and immunofluorescence assay ( IFA ) for p65 translocation to nuclei ( Fig. 2C ) ."
Momelotinib affects Primary Myelofibrosis
| 2
Momelotinib inhibits Primary Myelofibrosis. 2 / 2
| 2

medscan
"Genetic determinants of response and survival in momelotinib-treated patients with myelofibrosis."

medscan
"Genetic determinants of response and survival in momelotinib-treated patients with myelofibrosis"
| 2
| 2

reach
"A Phase I/II trial and subsequent long-term follow-up and extension study in patients with high- or intermediate-risk primary or post-PV/ET MF showed that the majority of evaluable patients treated with momelotinib had durable spleen response and symptom improvement, with a median treatment duration of 507 days."

reach
"XREF_BIBR In 100 consecutive patients with MF treated with momelotinib at the Mayo Clinic, presence of CALR mutations (hazard ratio 0.2, 95% confidence interval 0.04-0.6) and absence of ASXL1 mutations (hazard ratio 0.3, 95% confidence interval 0.1-0.8) were independently associated with better spleen response (as per International Working Group-Myeloproliferative Neoplasms Research and Treatment) in a multivariable analysis."
Momelotinib affects JAK3
1 | 1
1 | 1

reach
"28 Finally, momelotinib (also known as CYT-387) inhibits both JAK1 (IC 50 11 nm) and JAK2 (IC 50 18 nm), rather than JAK3 (IC 50 0.16 muM), although off-target effects (serine/threonine kinase IKBKE) have been described."

tas
No evidence text available
Momelotinib affects ACVR1
1 | 1
1 | 1

reach
"Momelotinib inhibits ACVR1 and ALK2, decreases hepcidin production, and ameliorates anemia of chronic disease in rodents."

tas
No evidence text available
Lestaurtinib affects virus genome copy
| 2
Lestaurtinib inhibits virus genome copy. 2 / 2
| 2

eidos
"Chaetocin , gemcitabine and lestaurtinib reduce virus genome copy numbers within treated cells ."
| PMC

eidos
"Fig. 4 : Chaetocin , gemcitabine and lestaurtinib reduce virus genome copy numbers within treated cells ."
| PMC
Lestaurtinib affects viral early late proteins
| 2
Lestaurtinib inhibits viral early late proteins. 2 / 2
| 2

eidos
"Chaetocin , gemcitabine and lestaurtinib reduce expression of viral early and late proteins ."
| PMC

eidos
"Fig. 3 : Chaetocin , gemcitabine and lestaurtinib reduce expression of viral early and late proteins ."
| PMC
Lestaurtinib affects late HAdV-4 HAdV-7
| 2
Lestaurtinib inhibits late HAdV-4 HAdV-7. 2 / 2
| 2

eidos
"Fig. 6 : Chaetocin , gemcitabine and lestaurtinib reduce late gene expression from HAdV-4 and HAdV-7 ."
| PMC

eidos
"Chaetocin , gemcitabine and lestaurtinib reduce late gene expression from HAdV-4 and HAdV-7 ."
| PMC
Dabrafenib affects ptc
| 2
| 2

reach
"In this study, BRAF V600E -mutant (BCPAP and K1) and BRAF-wild-type (TPC-1) PTC cells were treated with MAPKi (dabrafenib or selumetinib) or EZH2 inhibitor (tazemetostat), or in combination, and the expression of iodine metabolizing genes, radioiodine uptake, and toxicity were tested."

reach
"Dabrafenib can stimulate radioiodine uptake in patients with metastatic BRAF V600E-mutant iodine-refractory PTC, representing a potential new therapeutic approach for these patients."
Dabrafenib affects progression-free survival
| 2
Dabrafenib activates progression-free survival. 2 / 2
| 2

medscan
"The concurrent administration of dabrafenib and trametinib was associated with a higher incidence of complete response (9% vs. 4%) and longer progression-free survival (9.4 months vs. 5.8 months) compared to dabrafenib alone."

medscan
"Loss of p14ARF permits unregulated cell division while loss of p16INK4a leads to dysregulation of p53 and pervasive genetic instability. , In patients with late-stage BRAFV600E melanomas, BRAF inhibitors (for example, dabrafenib or vemurafenib) confer a survival advantage when compared with chemotherapy, demonstrating improvements in response-rates, progression-free survival and overall survival. , Initial responses to BRAF inhibitors are not durable, and patient relapse usually occurs within 6-7 months. , The use of concurrent BRAF and MEK inhibitors (for example, cobimetinib, selumetinib or trametinib) for patients with melanoma has been established as a synergistic treatment approach and one that has further improved response compared with BRAF monotherapy."

reach
"Dabrafenib suppressed the PolyP mediated vascular barrier permeability, upregulation of inflammatory biomarkers, adhesion and migration of leukocytes, and activation and/or production of nuclear factor-kappaB, tumor necrosis factor-alpha, and interleukin-6."

medscan
"Dabrafenib was further revealed to prevent acetaminophen-induced necrosis in normal human hepatocytes, which is considered to be mediated by RIP3."
Dabrafenib affects metastatic melanoma
| 2
Dabrafenib inhibits metastatic melanoma. 2 / 2
| 2

medscan
"Data from four published datasets were analyzed to determine whether preexisting MEK1(P124) mutations affect radiologic response or progression-free survival in patients with BRAF(V600)-mutant metastatic melanoma treated with vemurafenib or dabrafenib. 999997={Protein=673 Mutation=44999998} 44999998="V600" 44999999="P124"}"

medscan
"The BRAF gene, encoding for a protein member of the mitogen-activated-protein-kinase family [ ], is mutated in approximately half of all melanomas, and its mutations, commonly occurring at codon 600 (BRAFV600) [ , ], have been exploited to develop drugs (vemurafenib, dabrafenib and trametinib) effective against BRAF-driven metastatic melanoma [ - ]."

reach
"This result suggests that the effect of Dabrafenib on reduction of infarct volume is related to attenuated local inflammation after ischemic injury."

reach
"The suppressive effect of dabrafenib, a therapeutic agent for metastatic melanoma, in IgE mediated allergic inflammation."

reach
"Dabrafenib or enzalutamide, two CYP3A4 inducers, could significantly decrease hydroxychloroquine concentration during the first week of wash-out.Among pharmacodynamic interactions, QT interval prolongation could be of particular interest."
| PMC

eidos
"Dabrafenib or enzalutamide , two CYP3A4 inducers , could significantly decrease hydroxychloroquine concentration during the first week of wash-out ."
| PMC

reach
"In this model, combination of ATG7 deficiency and dabrafenib treatment significantly decreased melanoma tumor growth and induced senescence 29."

reach
"add another phenotype because, in this study, autophagy inhibition caused melanoma cell senescence, while also potentiating dabrafenib induced senescence."
Dabrafenib affects brain metastases
| 2
Dabrafenib inhibits brain metastases. 2 / 2
| 2

medscan
"There is no dominant site or pattern of disease progression in patients with brain metastases treated with dabrafenib."

medscan
"Dabrafenib has activity in patients with brain metastases, but little is known of the relative efficacy of treatment within and outside the brain."
Dabrafenib affects VCAM1
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Dabrafenib increases the amount of VCAM1. 2 / 2
2 |

ctd
No evidence text available

ctd
No evidence text available
Dabrafenib affects SELE
2 |
Dabrafenib increases the amount of SELE. 2 / 2
2 |

ctd
No evidence text available

ctd
No evidence text available
Dabrafenib affects PRC1
| 2
| 2

reach
"In agreement with the results obtained in 293T AS-CDK16 cells, dabrafenib promoted a dose dependent accumulation of PRC1 in the nuclear fraction, as demonstrated by western blot analysis and immunofluorescence studies."

reach
"Moreover, we observed that 2nM dabrafenib promoted PRC1 accumulation in HT-29 cells."
| 2

reach
"Structural analysis of the BRAF dimer complexes showed a considerable similarity of the inhibitor binding modes in the first monomer, while binding of PLX4720 and Dabrafenib to the second binding site produced a different interaction pattern (XREF_FIG)."

reach
"We also computed binding affinities and carried out alanine scanning of PLX4720 and Dabrafenib interactions in the second binding site (XREF_FIG)."
Dabrafenib affects PARP1
| 2
| 2

reach
"Figure XREF_FIG shows that at the indicated concentrations, Vemurafenib and Dabrafenib promoted PARP cleavage in CM2005.1, but not in CRMM1 and CRMM2."

reach
"PARP1 and caspase 3 cleavage patterns in SK-MEL-28VR1 cells treated with MTX + dabrafenib (lanes 12-15) indicated that caspase 3 is cleaved and activated by 24 hours after combination treatments (lane 12), but PARP1 is not cleaved at that time point."

reach
"In a multicenter phase II trial, 172 patients with BRAF mutant melanoma with at least one asymptomatic brain metastasis were treated with dabrafenib."

reach
"XREF_BIBR To the best of our knowledge, this is the first reported case of a BRAF V600E mutated lung adenocarcinoma with metastasis to the thyroid gland and treated with dabrafenib."
Dabrafenib affects ICAM1
2 |
Dabrafenib increases the amount of ICAM1. 2 / 2
2 |

ctd
No evidence text available

ctd
No evidence text available

reach
"Dr Girotti showed that BRAF inhibitors such as vemurafenib or dabrafenib, or MEK inhibitors, trametinib and cobimetinib, block the RAS-RAF-MEK-ERK pathway, inhibiting cell growth and increasing progression-free and overall survival in patients whose tumours carry BRAF mutations."

reach
"As a result, B-RAF inhibitors such as vemurafenib or dabrafenib, or MEK inhibitors such as trametinib, elicited striking clinical response rates when administered as single agents in patients with B-RAF V600E -mutant melanomas."
Dabrafenib affects Death
| 2
| 2

reach
"In similar randomized phase III trials, vemurafenib and dabrafenib each significantly reduced the risk of disease progression or death compared with dacarbazine in patients with previously untreated BRAF V600E-mutant MM (hazard ratio [HR]), 0.26 and 0.30, respectively; p <.001), clearly demonstrating the efficacy of BRAFi in this setting [12], [13]."

reach
"Recent data from the 2015 American Society of Clinical Oncology annual meeting confirmed the overall survival benefit from the trametinib and dabrafenib combination (a 29% reduction in risk of death) in the COMBI-d study, with reported median overall survival of 25.1 months for the combination arm versus 18.7 months in the dabrafenib only arm and a 2-year overall survival rate exceeding 50% for combined BRAF-MEK inhibitor therapy."
Dabrafenib affects CYCS
| 2
| 2

reach
"Only regorafenib started to trigger cytochrome c release at onefold Cmax, and two drugs, sorafenib and dabrafenib, caused cytochrome c release starting at fivefold Cmax."

reach
"The likely reason for this discrepancy is that dabrafenib also caused cytochrome c release leading to suppressed oxygen consumption."
Dabrafenib affects CDKN1A
| 2
Dabrafenib increases the amount of CDKN1A. 2 / 2
| 2

reach
"To further determine the p53 dependency of NEK9 inhibition following dabrafenib treatment, we evaluated the effects of both of the BRAF inhibitors upon isogenic p53 +/+ and p53-/- HCT116 cells and found that dabrafenib selectively inhibited pCHK1 and increased p21 expression in the cells that were p53-null."

reach
"To address the role of p53 in the anticancer effects of dabrafenib, we next treated p53 +/+ and -/- KRAS-mutant HCT116 cells with drug and found that dabrafenib, but not vemurafenib, induced p21 expression and inhibited pCHK1 in the p53-/- cells."
Dabrafenib affects BRAF inhibitors
| 2
Dabrafenib inhibits BRAF inhibitors. 2 / 2
| 2

reach
"5-7,9,10,13 A recent study following 51 patients with ECD treated with BRAF inhibitors demonstrated disease regression in all patients, with 1 patient treated with dabrafenib monotherapy from the beginning and 3 patients switched to dabrafenib from vemurafenib because of adverse effects."

reach
"To the authors ' knowledge, this study represents the largest genetic and genomics based examination of human melanoma tissue from patients treated with BRAF inhibitors, specifically patients treated with dabrafenib on the phase I/II trial, to identify correlates associated with response."
Brivanib affects growth factor
| 2
Brivanib inhibits growth factor. 2 / 2
| 2

medscan
"To determine whether brivanib inhibits growth factor-induced proliferation of hepatic stellate cells, we examined the effect of increasing concentrations of brivanib on LX-2 hepatic stellate cell proliferation under control conditions or after stimulation with concentrations of platelet-derived growth factor, VEGF, and FGF2 shown to induce LX-2 proliferation."

medscan
"Our findings demonstrate that brivanib reduces liver fibrosis in three different animal models, and inhibits growth factor-induced stellate cell proliferation and activation."
Brivanib affects FGF
| 2
Brivanib inhibits FGF. 2 / 2
| 2

medscan
"Our findings that brivanib inhibits not only VEGF- and fibroblast growth factor-mediated proliferation of hepatic stellate cells, but also inhibits platelet-derived growth factor-induced proliferation, together with our other findings that brivanib abrogates phosphorylation of the platelet-derived growth factorβ receptor, suggest the need to further characterize the modulation of platelet-derived growth factor signaling by brivanib."

medscan
"While brivanib inhibits VEGF and fibroblast growth factor, both of which are related to liver fibrosis, the effect of brivanib on liver fibrosis has not been previously studied."
Y-27632 affects Rho kinase (ROCK
| 2
Y-27632 inhibits Rho kinase (ROCK. 2 / 2
| 2

medscan
"This functional desensitization was blocked by the Rho kinase (ROCK) inhibitor, Y-27632, but not by Gq or Gs-pathway inhibitors or inhibition of β-arrestin recruitment."

medscan
"Treatment with the Rho kinase (ROCK) inhibitor Y-27632 caused a decrease in human microlymphatic endothelial cells of dermal origin barrier function."
Y-27632 affects Neoplasms
| 1 1
| 1 1

reach
"Unexpectedly, combination of feeder layers and Y-27632 allows to rapidly establish both normal and tumor cell cultures from non-keratinocyte tissues Suprynowicz et al. 2012; Palechor-Ceron et al. 2013; Liu et al. 2017) ."
| PMC

eidos
"Since then , Y-27632 , which is more effective in cancer , was developed and used on hPSCs ."
| 1 1
| 1 1

reach
"Y-27632 (10 µM, Sigma) was added for the first 48 hr of culture to promote cell survival."
| DOI

eidos
"Y-27632 ( 10 muM , Sigma ) was added for the first 48 hr of culture to promote cell survival ."
| DOI

medscan
"In conclusion, we demonstrated that CX4945 and LY2157299 exert relevant but distinct anticancer effects against human Cholangiocarcinoma cells, with CX4945 acting on cell viability and apoptosis, and LY2157299 impairing cell migration."

medscan
"In keeping with our results, in a hepatocellular carcinoma cell line, LY2157299 blocked cell migration by activating SMAD2, but independently from TGF-b receptors [ ]."
LY-2157299 affects TGFBR1
2 |
2 |

signor
No evidence text available

signor
"Ly2157299, a new type i receptor tgf-beta kinase antagonist, was"
LY-2157299 affects TGFBR
| 2
| 2

medscan
"Mechanism studies revealed that blockage of CAFs-secreted TGFβ1 signaling by its receptor TGFβR1 inhibitor LY2157299 significantly reversed the chemoresistance in vitro and in vivo."

medscan
"In keeping with our results, in a hepatocellular carcinoma cell line, LY2157299 blocked cell migration by activating SMAD2, but independently from TGF-b receptors [ ]."

medscan
"These results suggest that targeting the TGF-β signaling with a combination of CX-4945 and LY2157299 could have potential benefits in the treatment of human Cholangiocarcinoma."

medscan
"In conclusion, we demonstrated that CX4945 and LY2157299 exert relevant but distinct anticancer effects against human Cholangiocarcinoma cells, with CX4945 acting on cell viability and apoptosis, and LY2157299 impairing cell migration."
KW2449 affects MAP3K11
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2 |

tas
No evidence text available

tas
No evidence text available
KW2449 affects BCR
| 2
KW2449 inhibits BCR. 2 / 2
| 2

reach
"Although the multi-kinase inhibitor KW2449, which also inhibits Bcr and Abl and aurora kinases, has primarily been developed as a FLT3 inhibitor in AML [XREF_BIBR], preclinical studies demonstrate that it effectively kills Bcr and Abl + leukemias, including Ph + ALL, bearing gatekeeper mutations [XREF_BIBR]."

reach
"In IM resistant BV173 and E255K and Adult and T315I cells, coadministration of KW2449 with either vorinostat or SNDX clearly inhibited Bcr and Abl activation and reduced total expression, whereas single drug treatment minimally affected Bcr and Abl levels or activation status."
A-674563 affects cell cycle
| 2
A-674563 activates cell cycle. 2 / 2
| 2

reach
"Excluding the p53 and EGFR mutant cell lines, A-674563 induced significant cell cycle changes in all of the cell lines while MK-2206 only induced significant changes in the Stk11 wild-type NCI-H358 cells."

reach
"The significant cell cycle changes induced by A-674563 include a decrease in the proportion of cells in the G0/G1 phase and an increase in the proportion of cells in the S phase."
A-674563 affects TAOK1
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2 |

tas
No evidence text available

tas
No evidence text available
A-674563 affects PRKX
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2 |

tas
No evidence text available

tas
No evidence text available
A-674563 affects PRKG2
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2 |

tas
No evidence text available

tas
No evidence text available
A-674563 affects PRKG1
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2 |

tas
No evidence text available

tas
No evidence text available
A-674563 affects PRKD3
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2 |

tas
No evidence text available

tas
No evidence text available
A-674563 affects PRKCG
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2 |

tas
No evidence text available

tas
No evidence text available
A-674563 affects PRKACB
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2 |

tas
No evidence text available

tas
No evidence text available
A-674563 affects PKN2
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2 |

tas
No evidence text available

tas
No evidence text available
A-674563 affects PIM3
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2 |

tas
No evidence text available

tas
No evidence text available
A-674563 affects PIM2
2 |
2 |

tas
No evidence text available

tas
No evidence text available
A-674563 affects PIM1
2 |
2 |

tas
No evidence text available

tas
No evidence text available
A-674563 affects MINK1
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2 |

tas
No evidence text available

tas
No evidence text available
A-674563 affects MELK
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2 |

tas
No evidence text available

tas
No evidence text available
A-674563 affects MAP4K4
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2 |

tas
No evidence text available

tas
No evidence text available
A-674563 affects MAP4K2
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2 |

tas
No evidence text available

tas
No evidence text available
A-674563 affects HIPK4
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2 |

tas
No evidence text available

tas
No evidence text available
A-674563 affects HIPK2
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2 |

tas
No evidence text available

tas
No evidence text available
A-674563 affects FLT3
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2 |

tas
No evidence text available

tas
No evidence text available
A-674563 affects DAPK3
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2 |

tas
No evidence text available

tas
No evidence text available
A-674563 affects CSNK1G3
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2 |

tas
No evidence text available

tas
No evidence text available
A-674563 affects CSNK1G2
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2 |

tas
No evidence text available

tas
No evidence text available
A-674563 affects CSNK1G1
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2 |

tas
No evidence text available

tas
No evidence text available
A-674563 affects CSNK1D
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2 |

tas
No evidence text available

tas
No evidence text available
A-674563 affects CDC42BPA
2 |
2 |

tas
No evidence text available

tas
No evidence text available
A-674563 affects CAMK2G
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2 |

tas
No evidence text available

tas
No evidence text available
A-674563 affects CAMK2D
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2 |

tas
No evidence text available

tas
No evidence text available
A-674563 affects CAMK2B
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2 |

tas
No evidence text available

tas
No evidence text available
A-674563 affects AKT3
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2 |

tas
No evidence text available

tas
No evidence text available
| 1 1
Sotrastaurin inhibits PTPN22. 1 / 1
| 1

medscan
"Finally, we show that PTPN22 can be effectively down-regulated by the PKC inhibitors ruboxistaurin and sotrastaurin, resulting in enhanced killing of chronic lymphocytic leukemia cells exposed to proapoptotic B-cell receptor stimuli."

reach
"Finally, we show that PTPN22 can be effectively down-regulated by the PKC inhibitors ruboxistaurin and sotrastaurin, resulting in enhanced killing of CLL cells exposed to proapoptotic BCR stimuli."
| 2
| 1

medscan
"AEB071 significantly slowed the growth of tumors in an allograft model of GNAQ(Q209L)-transduced melanocytes, but did not induce tumor shrinkage. 46999999="Q209L"}"
Sotrastaurin activates Neoplasms.
| 1

medscan
"The combination treatment of AEB071 and MEK162 led to a significant reduction of tumor growth compared to monotherapy with either compound in a dose dependent manner."

medscan
"Protein kinase C inhibitor sotrastaurin selectively inhibits the growth of CD79 mutant diffuse large B-cell lymphomas."

medscan
"We found that sotrastaurin produced significant antitumor effects in a mouse xenograft model of CD79A/B-mutated diffuse large B-cell lymphoma."
| 2
Sotrastaurin increases the amount of Cyclin.
| 1
Sotrastaurin increases the amount of Cyclin. 1 / 1
| 1

reach
"AEB071 mediated cell inhibition in the GNAQ mutated UM was accompanied by inhibition of Erk1/2 phosphorylation, NF-kappaB, decreased expression of cyclin D1, survivin, Bcl-xL and XIAP, and increased expression of cyclin dependent kinase inhibitor p27 Kip1."
Sotrastaurin decreases the amount of Cyclin.
| 1
Sotrastaurin decreases the amount of Cyclin. 1 / 1
| 1

reach
"The absence of increased efficacy after AEB071 + LEE011 combination could be in part explained by the fact that AEB071 decreases expression of cyclin D1 and Rb proteins and induces G1/S cell cycle arrest [XREF_BIBR] [XREF_BIBR] [XREF_BIBR], effects that are specific to CDK4/6 targeting."
| 2
Sotrastaurin decreases the amount of CDKN1B.
| 1
Sotrastaurin decreases the amount of CDKN1B. 1 / 1
| 1

reach
"AEB071 mediated cell inhibition in the GNAQ mutated UM was accompanied by inhibition of Erk1/2 phosphorylation, NF-kappaB, decreased expression of cyclin D1, survivin, Bcl-xL and XIAP, and increased expression of cyclin dependent kinase inhibitor p27 Kip1."
Sotrastaurin activates CDKN1B.
| 1
| 1

reach
"In agreement with this G1 arrest, AEB071 also significantly increased the accumulation of p27 Kip1, while decreasing the expression of cylin D1 in all three GNAQ mutated cell lines tested (XREF_FIG)."
Momelotinib affects STAT
| 2
Momelotinib inhibits STAT.
| 1
| 1

reach
"Conversely, JAK and STAT signaling was selectively activated in CBL iPSCs and abrogated by the JAKi momelotinib and ruxolitinib."
Momelotinib activates STAT.
| 1
| 1

reach
"Momelotinib therapy targets the JAK and STAT family, a key prosurvival pathway that controls apoptotic signals in hematological malignancies [XREF_BIBR]."
| 2
Momelotinib inhibits LY6G6D.
| 1
| 1

reach
"Momelotinib, an inhibitor of JAK1 and JAK2, consistently abrogated the STAT5 and LY6G6D axis in vitro, sensitizing MSS cancer cells with an intact JAK-STAT signaling, to efficiently respond to trametinib, a MEK inhibitor used in clinical setting."
Momelotinib decreases the amount of LY6G6D.
| 1
Momelotinib decreases the amount of LY6G6D. 1 / 1
| 1

reach
"We observed that momelotinib vigorously inhibited both STAT5 activation and endogenous LY6G6D expression."
Dabrafenib affects phospho-MEK
| 2
Dabrafenib inhibits phospho-MEK.
| 1
Dabrafenib inhibits phospho-MEK. 1 / 1
| 1

reach
"Dabrafenib induced significant phospho-MEK and -ERK activation at concentrations up to 1 muM and inhibited the phospho-MEK and -ERK at a high concentration of 10 muM."
Dabrafenib activates phospho-MEK.
| 1
Dabrafenib activates phospho-MEK. 1 / 1
| 1

reach
"Dabrafenib induced significant phospho-MEK and -ERK activation at concentrations up to 1 muM and inhibited the phospho-MEK and -ERK at a high concentration of 10 muM."
Dabrafenib affects iodide
| 2
Dabrafenib inhibits iodide.
| 1
| 1

reach
"Moreover, dabrafenib rather than another clinically used B-Raf inhibitor vemurafenib (with poor RIP3 inhibitory activity) reversed the loss of propidium iodide (PI)-negative HT29 cells caused by TSZ (XREF_SUPPLEMENTARY)."
Dabrafenib activates iodide.
| 1
| 1

reach
"For BRAF mutant patients, treatment with a BRAF inhibitor may be a more promising approach : a recent pilot trial showed that Dabrafenib increased iodide incorporation in 6 of 10 BRAF mutant patients, resulting in tumor shrinkage after subsequent treatment with I-131 in 5 of the 6 patients (2 partial responses and 4 patients with stable disease)."
| 2
Dabrafenib decreases the amount of diiodine.
| 1
Dabrafenib decreases the amount of diiodine. 1 / 1
| 1

reach
"Compared to BRAF wild-type BHP 2-7 cells, BRAF inhibitor dabrafenib preferentially inhibited ERK signaling and thyroid cancer cell proliferation, arrested cell circle, and regulated iodine and glucose handling gene expression in BRAF V600E -positive PTC cells."
Dabrafenib activates diiodine.
| 1
| 1

reach
"XREF_BIBR, XREF_BIBR Selumetinib, a selective inhibitor of MEK1 and MEK2, and dabrafenib, a selective potent BRAFV600E inhibitor, had induced radioactive iodine uptake in a subset of patients with RAI-refractory disease and retreatment with RAI."
| 2
| 1

reach
"In preclinical studies, there is strong evidence for the interaction of vemurafenib, dabrafenib, trametinib, palbociclib, cobimetinib and omipalisib with P-gp and BCRP."
Dabrafenib activates cobimetinib.
| 1

reach
"Additional compounds and antibodies for targeted, immuno- as well as combination therapy have been and are currently being developed such as the BRAF V600mut inhibitor dabrafenib [XREF_BIBR], mitogen activated protein kinase kinase (MEK) inhibitors trametinib [XREF_BIBR] and cobimetinib [XREF_BIBR], the anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody ipilimumab [XREF_BIBR] as well as anti-programmed cell death protein 1 (PD-1) antibodies pembrolizumab [XREF_BIBR] and nivolumab [XREF_BIBR]."
Dabrafenib affects casE
| 2
Dabrafenib binds casE.
| 1

reach
"Prospective Case Series of Cutaneous Adverse Effects Associated With Dabrafenib and Trametinib."
Dabrafenib activates casE.
| 1
| 1

reach
"Cardiac tamponade induced by dabrafenib and trametinib combination therapy for melanoma : Case report."
Dabrafenib affects STING1
| 1 1
Dabrafenib phosphorylates STING1.
| 1
Dabrafenib leads to the phosphorylation of STING1. 1 / 1
| 1

reach
"As speculated, combined treatment of Dabrafenib or Vemurafenib with diABZI, enhanced phosphorylation of STING (XREF_FIG) and IRF3 (XREF_FIG)."
Dabrafenib activates STING1.
| 1
| 1

eidos
"Combination of diABZI and BRAF Inhibitors Activate STING and Prevent NRF2 Translocation Since we observed that diABZI potently activates STING pathway and prevents NRF2 activation , we investigated if the combination of diABZi with the currently available BRAFis ; Dabrafenib and Vemurafenib will also activate STING and inhibit NRF2 ."
Dabrafenib affects SLC5A5
| 1 1
Dabrafenib increases the amount of SLC5A5.
| 1
Dabrafenib increases the amount of SLC5A5. 1 / 1
| 1

reach
"Western blot analysis demonstrated that dabrafenib restored the expression of NIS, Tg, TSHR, and TPO, and reduced the expression of GLUT1 in both BCPAP and K1 cells."
Dabrafenib activates SLC5A5.
| 1
| 1

medscan
"Western blot analysis demonstrated that dabrafenib restored the expression of NIS, thyroglobulin, TSHR, and thyroperoxidase, and reduced the expression of GLUT1 (Figure ) in both BCPAP and K1 cells."
Dabrafenib affects JNK
| 2
Dabrafenib phosphorylates JNK.
| 1
Dabrafenib leads to the phosphorylation of JNK. 1 / 1
| 1

reach
"Dabrafenib was found to inhibit apoptosis, and to enhance the phosphorylation of extracellular signal regulated kinase (ERK), and inhibit the phosphorylation of c-Jun NH2-terminal kinase."
Dabrafenib inhibits JNK.
| 1
| 1

reach
"We have shown that at clinically relevant doses, vemurafenib, but not dabrafenib, potently inhibits JNK signaling and suppresses apoptosis, which cooperates with paradoxical ERK activation to induce tumors [XREF_BIBR]."
| 1 1
Dabrafenib inhibits Caspase.
| 1
| 1

medscan
"Similar in HT29 cells, dabrafenib rather than vemurafenib or GDC0879 prevented the caspase inhibitor z-VAD-induced necroptosis in RIP3-proficient N cells or shNC N cells ( and (right))."
Dabrafenib activates Caspase.
| 1
| 1

reach
"In combination with Trametinib, both Dabrafenib and AZ628 increased caspase 3/7 activity compared to controls and single agents, and this effect was greatest after treatment with AZ628 plus Trametinib."

reach
"However, since differentiated hAEC cultures cannot be reliably established after monolayer passage two due to cellular senescence and loss of differentiation potential [16] we had to devise a method that would prolong the lifespan of primary human cells in monolayer culture to allow for lentiviral transduction, expansion and eventual cell sorting.Treatment of both bronchial and cervical epithelial cells with a commercially available ROCK inhibitor, Y-27632, has been shown to induce a basal epithelial cell phenotype, thereby preserving the differentiation capabilities of human epithelial cells in vitro [18]."
Y-27632 activates cell differentiation.
| 1
Y-27632 activates cell differentiation. 1 / 1
| 1

medscan
"Treatment with Y-27632 also enhanced the osteoblastic differentiation of cultured murine neonatal calvarial cells."
Y-27632 affects MSN
| 2
Y-27632 inhibits MSN.
| 1
Y-27632 inhibits MSN. 1 / 1
| 1

medscan
"Although Y-27632 prevented the increase in phosphorylated moesin, consistent with ERM proteins being substrates for ROCK ( ; ; ), it had no effect on the increased abundance of total moesin protein."
Y-27632 decreases the amount of MSN.
| 1
Y-27632 decreases the amount of MSN. 1 / 1
| 1

medscan
"Y-27632 reduced the expression levels of phosphorylated ezrin, radixin, and moesin in angiotensin II-treated Wistar-Kyoto rats and spontaneously hypertensive rats."
| 1 1
Y-27632 inhibits Hypertension. 1 / 1
| 1

medscan
"Consistent with this idea is the observation that ROCK inhibitor Y-27632 reduces hypertension , and that the Ras-homology/ROCK signaling pathway in smooth muscle cells is an important contributor to peripheral resistance ."

eidos
"Y-27632 also suppresses formation of stress fibers in cultured cells and decreases hypertension in several hypertensive rat models [ 109,110,111 ] ."
| 1 1
LY-2157299 activates angiogenesis. 1 / 1
| 1

reach
"In vivo, LY-2157299 induced angiogenesis and enhanced VEGF- and basic-fibroblast-growth-factor-induced angiogenesis in a Matrigel-plug assay, whereas adding an alpha5-integrin-neutralizing antibody to the Matrigel selectively inhibited this enhanced response."

medscan
"In vivo, LY-2157299 induced angiogenesis and enhanced VEGF- and basic-fibroblast-growth-factor-induced angiogenesis in a Matrigel-plug assay, whereas adding an alpha5-integrin-neutralizing antibody to the Matrigel selectively inhibited this enhanced response."
LY-2157299 affects TGFB1
| 1 1
| 1

medscan
"Conversely, we observed that inhibition of the TGFβ signaling pathway by LY2157299, a TGFβRI kinase inhibitor, enhanced sorafenib-induced apoptosis, in vitro."
LY-2157299 inhibits TGFB1. 1 / 1
| 1

reach
"Our results showed that TGF-beta1 up-regulated p-Smad2, p-Smad3, Beclin 1 and LC3beta-II/I conversion in Star treated NIH3T3 fibroblast, but TGF-betaR1 and ALK5 inhibitor LY-2157299 suppressed the upregulation effects of TGF-beta1."

reach
"Specifically, both vorinostat and SNDX-275 potentiated KW2449 induced ROS formation in both IM sensitive and IM resistant mutant cells, and the lethality of HDACI and KW2449 regimens, was significantly attenuated by the antioxidant TBAP."

reach
"HDACIs promote KW2449 mediated ROS generation and DNA damage in IM sensitive and -resistant Bcr and Abl + leukemia cells."
| 1

reach
"KW2449 significantly reduced the viability of wildtype-PTEN cells causing apoptosis, while little effect was observed in mutant-PTEN counterparts."
| 1

reach
"KW2449 interacts synergistically with HDACIs to induce apoptosis in Ph + CML cells in a time- and concentration dependent manner."
KW2449 affects Histone_H3
| 2
KW2449 dephosphorylates Histone_H3.
| 1
KW2449 leads to the dephosphorylation of Histone_H3. 1 / 1
| 1

reach
"As previously reported [XREF_BIBR], KW2449 moderately reduced phosphorylation of histone H3, an indicator of aurora B activity, in nocodozole treated K562 cells (XREF_SUPPLEMENTARY)."
KW2449 decreases the amount of Histone_H3.
| 1
KW2449 decreases the amount of Histone_H3. 1 / 1
| 1

reach
"Although in the present study, KW2449 alone diminished expression of phospho-histone H3, consistent with previous reports [XREF_BIBR], potentiation of this effect by HDACIs was not observed."
KW2449 affects AKT
| 2
KW2449 leads to the phosphorylation of AKT on S473. 1 / 1
| 1

reach
"We found that KW2449 caused a dose dependent, biphasic induction of AKT phosphorylation at Ser473 in mutant-PTEN cells."
KW2449 leads to the phosphorylation of AKT. 1 / 1
| 1

reach
"Co-treatment with the inhibitors of its upstream signaling completely abolished the reactivation of AKT phosphorylation by KW2449 and reversed the drug resistant phenotype."
A-674563 affects AKT2
| 2
A-674563 increases the amount of AKT2.
| 1
A-674563 increases the amount of AKT2. 1 / 1
| 1

reach
"A-674563 also increased p-AKT-1 and p-AKT-2 expression in the A549 cells and increased expression over time in the A427 cells."
A-674563 activates AKT2.
| 1
A-674563 activates AKT2. 1 / 1
| 1

reach
"Thus, A-674563 may only be increasing AKT-2 activity in the A427 cells."
Sotrastaurin affects tacrolimus inasmuch
| 1
Sotrastaurin activates tacrolimus inasmuch. 1 / 1
| 1

eidos
"158 Sotrastaurin increased tacrolimus concentration inasmuch as the tacrolimus dose needed to achieve a given C 0 was up to 47 % lower when combined with sotrastaurin versus MMF ."
| PMC

reach
"Mantle cell lymphoma is an aggressive malignancy supported by aberrant B cell receptor (BCR) signaling, which is targeted by inhibitors ibrutinib and sotrastaurin."
Sotrastaurin affects recovered cell culture media
| 1
Sotrastaurin activates recovered cell culture media. 1 / 1
| 1

eidos
"( A ) Graph depicts effect of sotrastaurin ( 10-5-10-8 M ) on ACE2 activity recovered from cell culture media ."
| 1

reach
"The treatment of SH-SY5Y cells with either a MAPK and ERK kinase 1/2 specific inhibitor (1,4-diamino-2, 3-dicyano-1,4-bis (2-aminophenylthio) butadine) or a protein kinase C inhibitor (sotrastaurin) blocked the effects of raloxifene on the phosphorylation of ERK1/2 and the regulation of AVP mRNA levels."
Sotrastaurin affects pMEK
| 1
Sotrastaurin inhibits pMEK. 1 / 1
| 1

reach
"Using two different MEK inhibitors, we found that pMEK accumulation in response to MEK inhibition can be abrogated by the addition of the PKC inhibitor AEB071 (XREF_FIG and XREF_SUPPLEMENTARY) in the GNAQ/11 mutant cells, but not melanoma cell lines without GNAQ/11 mutations."
| 1

medscan
"The protein kinase C inhibitor sotrastaurin markedly potentiates the inhibition of ribosomal RNA synthesis, PCNA expression, and T-cell activation induced by Mycophenolic acid, suggesting that the combination of the two agents are more highly effective than either alone in inducing immunosuppression."
Sotrastaurin affects nPKC isoforms
| 1
Sotrastaurin inhibits nPKC isoforms. 1 / 1
| 1

reach
"One of the most potent and clinically advanced PKC inhibitors is AEB071, which selectively inhibits cPKC and nPKC isoforms."

reach
"Moreover, inhibitor of morphine (naltrexone) or PKC-theta (AEB071) can reverse morphine induced Th2 cell differentiation."
Sotrastaurin affects mAPOBEC3
| 1
Sotrastaurin inhibits mAPOBEC3. 1 / 1
| 1

reach
"Consistent with a role for TNFalpha in T cell mediated mAPOBEC3 induction in tumor cells, exogenous TNFalpha was sufficient to induce mAPOBEC3 (XREF_FIG and XREF_FIG), an effect which was almost completely inhibited by AEB071 action upon the tumor cells themselves (XREF_FIG)."
Sotrastaurin affects expression
| 1
Sotrastaurin inhibits expression. 1 / 1
| 1

sparser
"AEB071 further inhibited the expression of the anti-apoptotic proteins survivin, Bcl-xL and XIAP in a dose-dependent manner in Mel202, 92.1 and Omm1.3 cells ( xref )."

reach
"These assays revealed that AEB071 pretreatment did not enhance or reduce Treg mediated suppression of T cell proliferation (DMSO CD25 + versus AEB CD25 + in XREF_FIG)."

sparser
"Furthermore, AEB071 markedly inhibited lymphocyte function-associated antigen-1-mediated T-cell adhesion at nanomolar concentrations."
Sotrastaurin affects catalytic activity
| 1
Sotrastaurin inhibits catalytic activity. 1 / 1
| 1

sparser
"Upon T-cell stimulation, AEB071 markedly inhibited in situ PKC catalytic activity and selectively affected both the canonical nuclear factor-kappaB and nuclear factor of activated T cells (but not activator protein-1) transactivation pathways."

reach
"AEB071 inhibits not only PKCtheta, but also other novel (Ca 2+ -independent delta, epsilon, and eta; nPKC) and conventional (Ca 2+ -dependent alpha and beta; cPKC) members at sub-nanomolar to low nanomolar concentrations, with a 1,000-10,000-fold lower selectivity for other kinases."
Sotrastaurin affects cPKC
| 1
Sotrastaurin inhibits cPKC. 1 / 1
| 1

reach
"One of the most potent and clinically advanced PKC inhibitors is AEB071, which selectively inhibits cPKC and nPKC isoforms."
Sotrastaurin affects branching
| 1
Sotrastaurin inhibits branching. 1 / 1
| 1

medscan
"AEB071, an inhibitor of protein kinase Cθ kinase activity, also inhibits growth and invasive branching of triple-negative breast cancer cells in 3-D cultures, further supporting a role for protein kinase Cθ kinase activity in triple-negative cancer cell growth."
Sotrastaurin affects autophosphorylation
| 1
Sotrastaurin inhibits autophosphorylation. 1 / 1
| 1

sparser
"We confirmed that treatment of MDA-231-Luc-D3H2LN cells with AEB071 inhibited PKCθ autophosphorylation at Threonine 538, even at doses as low as 100 nM (Fig.  xref )."
Sotrastaurin affects activation PKCtheta TBK1
| 1
Sotrastaurin activates activation PKCtheta TBK1. 1 / 1
| 1

eidos
"In agreement with these findings , PKCtheta was activated by EGF , insulin , and FBS , and the PKC inhibitor Sotrastaurin impaired the activation of PKCtheta and TBK1 ( Fig. 4d and Extended Data Fig. 6f , g ) ."
Sotrastaurin affects XIAP
| 1
Sotrastaurin decreases the amount of XIAP. 1 / 1
| 1

reach
"AEB071 further inhibited the expression of the anti-apoptotic proteins survivin, Bcl-xL and XIAP in a dose dependent manner in Mel202, 92.1 and Omm1.3 cells (XREF_FIG)."
Sotrastaurin affects Treg
| 1
Sotrastaurin inhibits Treg. 1 / 1
| 1

reach
"This is also supported by the observation that AEB071, an inhibitor of protein kinase C-theta that preferentially halts Treg differentiation and activation, preserves graft survival and GVL but prevents IFN-gamma production and GVHD by enhancing the function of Treg."
Sotrastaurin affects Tconv
| 1
Sotrastaurin inhibits Tconv. 1 / 1
| 1

reach
"However, AEB071 was fully able to suppress Tconv activation when included in the cultures throughout, implying a reversibel nature of AEB071."
Sotrastaurin affects TCR
| 1
| 1

reach
"Sotrastaurin, a PKC-Theta inhibitor, was utilized to block NF-kappaB activation following TCR engagement, and was found to significantly inhibit TCR mediated chemotherapy resistance in T8ML-1 and in most primary TCL cells (XREF_SUPPLEMENTARY)."
Sotrastaurin affects TBK1
| 1
| 1

reach
"In agreement with these findings, PKCtheta was activated by EGF, insulin, and FBS, and the PKC inhibitor Sotrastaurin impaired the activation of PKCtheta and TBK1 (XREF_FIG and XREF_FIG, XREF_FIG)."
Sotrastaurin affects STK3
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1 |

tas
No evidence text available
Sotrastaurin affects SLK
1 |
1 |

tas
No evidence text available
Sotrastaurin affects SGK2
1 |
1 |

tas
No evidence text available
Sotrastaurin affects SGCB
| 1
Sotrastaurin decreases the amount of SGCB. 1 / 1
| 1

reach
"In particular, although AEB071 downregulated A3B expression, this was not the case for MYBL2, indicating that at least two parallel signal pathways act synergistically to regulate A3B expression in human cells (XREF_FIG)."
Sotrastaurin affects S473-Akt
| 1
Sotrastaurin leads to the dephosphorylation of S473-Akt. 1 / 1
| 1

reach
"In the presence of ATO, idelalisib and sotrastaurin significantly reduced the stroma induced phosphorylation of S473-Akt, IkappaB and STAT3."
1 |

tas
No evidence text available
1 |

tas
No evidence text available
Sotrastaurin affects RB1
| 1
Sotrastaurin decreases the amount of RB1. 1 / 1
| 1

reach
"The absence of increased efficacy after AEB071 + LEE011 combination could be in part explained by the fact that AEB071 decreases expression of cyclin D1 and Rb proteins and induces G1/S cell cycle arrest [XREF_BIBR] [XREF_BIBR] [XREF_BIBR], effects that are specific to CDK4/6 targeting."
1 |

ctd
No evidence text available
| 1

reach
"Co-targeting the NF-kappaB pathway with inhibitors of IKKalpha and beta (BMS-345541) or proteasome (bortezomib and carfilzomib) but not the pan-PKC inhibitor sotrastaurin provided exceptional synergistic cytotoxicity with IBR+VEN in these cell lines (XREF_SUPPLEMENTARY), at pharmacologically relevant concentrations 49 (XREF_FIG; XREF_SUPPLEMENTARY)."
| 1

reach
"In all models, GNAQ/11 mutated and wt, AEB071 treatment led to decreased pMARCKS and pPKCdelta."
1 |
1 |

tas
No evidence text available
1 |
1 |

tas
No evidence text available
1 |
1 |

tas
No evidence text available
1 |

tas
No evidence text available
Sotrastaurin affects PLK1
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1 |

tas
No evidence text available
Sotrastaurin affects PKN2
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1 |

tas
No evidence text available
Sotrastaurin affects PKCs
| 1
Sotrastaurin inhibits PKCs. 1 / 1
| 1

reach
"Since it reportedly does not inhibit Ca 2+ signaling, combination therapy with other immunosuppressive agents such as cyclosporine A at low, suboptimal concentrations may be useful, provided it does not cause global, potentially harmful immunosuppression It has been argued that the ability of AEB071 to broadly inhibit PKCs underlies its inhibition of T cell activation, since this broad activity prevents potential compensation by other PKC isoforms."
Sotrastaurin affects PKCetaat
| 1
Sotrastaurin inhibits PKCetaat. 1 / 1
| 1

reach
"AEB071 blocks the catalytic activity of PKCalpha, PKCbeta and PKCtheta isoforms at a low picomolar concentration range, as well as PKCdelta, PKCepsilon and PKCetaat higher, nanomolar, concentrations [XREF_BIBR]."
Sotrastaurin affects PKCalpha, beta, delta
| 1
Sotrastaurin inhibits PKCalpha, beta, delta. 1 / 1
| 1

reach
"These findings suggest that AEB071 may have greater overall inhibitory effect on multiple PKC isoforms in UM cells with mutated GNAQ : PKCalpha, beta, delta, epsilon and/or theta expression was suppressed by AEB071 in GNAQ mutated cells while PKCalpha, and PKCdelta and PKCepsilon expression was affected in GNAQ wild type cells."
Sotrastaurin affects PKCalpha and delta
| 1
Sotrastaurin decreases the amount of PKCalpha and delta. 1 / 1
| 1

reach
"As the expression of PKCalpha and delta was suppressed by AEB071 in both GNAQ wild type and mutated UM cells, we next investigated if these isoforms were of functional importance for UM cells by shRNA mediated knockdown to better understand the mechanisms for the differential AEB071 response in GNAQ wild type and mutated cells."
Sotrastaurin affects PKC-NF-kappaB
| 1
Sotrastaurin inhibits PKC-NF-kappaB. 1 / 1
| 1

reach
"Inhibition of PKC-NF-kappaB signaling by AEB071 during VSV-GFP or VSV-IFN-beta infection significantly inhibited the outgrowth of resistant colonies (XREF_FIG A)."
Sotrastaurin affects PKC kinase
| 1
Sotrastaurin inhibits PKC kinase. 1 / 1
| 1

reach
"Thus, some other PKC besides PKCtheta or PKCalpha, or even a non PKC kinase that is not inhibited by AEB071, may be important."
Sotrastaurin affects PIM3
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1 |

tas
No evidence text available
Sotrastaurin affects PIM2
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1 |

tas
No evidence text available
Sotrastaurin affects PCNA
| 1
Sotrastaurin decreases the amount of PCNA. 1 / 1
| 1

medscan
"The protein kinase C inhibitor sotrastaurin markedly potentiates the inhibition of ribosomal RNA synthesis, PCNA expression, and T-cell activation induced by Mycophenolic acid, suggesting that the combination of the two agents are more highly effective than either alone in inducing immunosuppression."
| 1
| 1

reach
"In all of the six representative GNAQ/11 mutated cell lines, AEB071 slightly induced cPARP."
| 1

reach
"So far the OMM1 cell line is the only exception of all GNAQ/11 mutated cell lines tested in which Sotrastaurin does not significantly enhance the Nutlin-3 effect."

reach
"In the Transwell invasion experiment, when the A549 cells were treated with Cal or AEB071 alone, the cell invasion ability was decreased to 59.78 and 48.60%, compared with the TPA induced group."
1 |
1 |

tas
No evidence text available
| 1

medscan
"protein kinase C inhibition with AEB071 or AHT956 suppressed protein kinase C and MAPK signalling and induced G1 arrest selectively in melanoma cell lines carrying GNAQ or GNA11 mutations."
1 |
1 |

tas
No evidence text available
Sotrastaurin affects MSC
| 1
| 1

reach
"Addition of tacrolimus, rapamycin or sotrastaurin to the lysis assay did not inhibit MSC killing."
1 |
1 |

tas
No evidence text available
Sotrastaurin affects MDM2-p53
| 1
Sotrastaurin binds MDM2-p53. 1 / 1
| 1

reach
"Recently, it has been shown that the combination of an inhibitor of the MDM2-p53 interaction (CGM097 14) with the broad PKC inhibitor Sotrastaurin did not achieve synergistic inhibition of cell growth in vitro 11."
1 |

tas
No evidence text available
1 |

tas
No evidence text available
Sotrastaurin affects IKKalpha/beta
| 1
Sotrastaurin activates IKKalpha/beta. 1 / 1
| 1

reach
"Co-targeting the NF-kappaB pathway with inhibitors of IKKalpha and beta (BMS-345541) or proteasome (bortezomib and carfilzomib) but not the pan-PKC inhibitor sotrastaurin provided exceptional synergistic cytotoxicity with IBR+VEN in these cell lines (XREF_SUPPLEMENTARY), at pharmacologically relevant concentrations 49 (XREF_FIG; XREF_SUPPLEMENTARY)."
Sotrastaurin affects IKB
| 1
Sotrastaurin leads to the phosphorylation of IKB. 1 / 1
| 1

reach
"In the presence of ATO, idelalisib and sotrastaurin significantly reduced the stroma induced phosphorylation of S473-Akt, IkappaB and STAT3."
1 |
1 |

tas
No evidence text available
Sotrastaurin affects GRK5
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1 |

tas
No evidence text available
| 1
Sotrastaurin inhibits mutated GNA11. 1 / 1
| 1

reach
"The PKC inhibitors AEB071 and AHT956 selectively inhibit the growth of GNAQ or GNA11 mutant melanoma cell lines."
Sotrastaurin affects G1 arrest
| 1
Sotrastaurin activates G1 arrest. 1 / 1
| 1

medscan
"protein kinase C inhibition with AEB071 or AHT956 suppressed protein kinase C and MAPK signalling and induced G1 arrest selectively in melanoma cell lines carrying GNAQ or GNA11 mutations."
Sotrastaurin affects FUT2
| 1
| 1

reach
"Further, SEC2 and ST-4-induced changes in PKCtheta and NF-kappaB signaling were significantly relieved by AEB071 in a dose dependent manner."
Sotrastaurin affects FER
1 |
1 |

tas
No evidence text available
| 1
Sotrastaurin leads to the dephosphorylation of EIF4EBP1. 1 / 1
| 1

reach
"Sotrastaurin decreased the expression of pro survival protein myeloid cell leukemia (MCL-1) and the phosphorylation of eukaryotic initiation factor 4E binding protein 1 (4E-BP1), both of which are downstream effectors of PIM-1."
| 1
Sotrastaurin leads to the dephosphorylation of EIF4E. 1 / 1
| 1

reach
"Sotrastaurin decreased the expression of pro survival protein myeloid cell leukemia (MCL-1) and the phosphorylation of eukaryotic initiation factor 4E binding protein 1 (4E-BP1), both of which are downstream effectors of PIM-1."
Sotrastaurin affects EGF-stimulated association TBK1 CARD10 PKCtheta
| 1
Sotrastaurin activates EGF-stimulated association TBK1 CARD10 PKCtheta. 1 / 1
| 1

eidos
"Interestingly , the PKC inhibitor Sotrastaurin inhibited EGF-stimulated association of TBK1 with CARD10 and PKCtheta , although it did not affect the constitutive TBK1-TBKBP1 binding ( Fig. 5j ) ."
Sotrastaurin affects EGF
| 1
| 1

reach
"Interestingly, the PKC inhibitor Sotrastaurin inhibited EGF stimulated association of TBK1 with CARD10 and PKCtheta, although it did not affect the constitutive TBK1-TBKBP1 binding (XREF_FIG)."

reach
"However, in the presence of ATO, idelalisib and sotrastaurin significantly reduced CLL cell viability in a dose dependent manner, while UO126 behave as the control with no inhibitors."
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tas
No evidence text available
Sotrastaurin affects CD86
| 1
Sotrastaurin decreases the amount of CD86. 1 / 1
| 1

reach
"Sotrastaurin did not inhibit B-cell proliferation, CD80 and CD86 expression, and IgG production and had only minor effects on IgM levels at the highest concentration administered."
Sotrastaurin affects CD80
| 1
Sotrastaurin decreases the amount of CD80. 1 / 1
| 1

reach
"Sotrastaurin did not inhibit B-cell proliferation, CD80 and CD86 expression, and IgG production and had only minor effects on IgM levels at the highest concentration administered."
Sotrastaurin affects CD8 T-cell function
| 1
Sotrastaurin inhibits CD8 T-cell function. 1 / 1
| 1

eidos
"4Amay indeed be the result of reduced induction of APOBEC3 in the tumor cells through inhibition of PKC signaling ( Fig. 4E ) , and / or the result of partial inhibition of CD8 + T-cell function by AEB071 ."
Sotrastaurin affects CD69
| 1
Sotrastaurin increases the amount of CD69. 1 / 1
| 1

reach
"The PKCtheta inhibitor AEB071 significantly suppressed SEC2 and ST-4-induced T cell proliferation, CD69 and CD25 expression, and IL-2 secretion with or without MHC II+ APCs."
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tas
No evidence text available
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tas
No evidence text available
| 1
Sotrastaurin decreases the amount of BIRC5. 1 / 1
| 1

reach
"AEB071 further inhibited the expression of the anti-apoptotic proteins survivin, Bcl-xL and XIAP in a dose dependent manner in Mel202, 92.1 and Omm1.3 cells (XREF_FIG)."
| 1
Sotrastaurin decreases the amount of BCL2A1. 1 / 1
| 1

reach
"Moreover, idelalisib and sotrastaurin did not significantly reduce the expression of Bcl-xL, Bcl-2 or Bfl-1, suggesting a role for Mcl-1 in the resistance to ATO induced by stroma."
Sotrastaurin affects BCL2
| 1
Sotrastaurin decreases the amount of BCL2. 1 / 1
| 1

reach
"Moreover, idelalisib and sotrastaurin did not significantly reduce the expression of Bcl-xL, Bcl-2 or Bfl-1, suggesting a role for Mcl-1 in the resistance to ATO induced by stroma."
| 1
Sotrastaurin decreases the amount of APOBEC3B. 1 / 1
| 1

reach
"Indeed, a clear dose dependent response was observed and, importantly, AEB071 caused a complete suppression of APOBEC3B expression at 500 nM, which is approximately 10-fold more potent than Go6983, BIM-1, or Go6983, consistent with reported lower IC50 values for this molecule (XREF_FIG)."
Sotrastaurin affects AP1
| 1
| 1

reach
"Furthermore, the PKC-theta inhibitor AEB071 inhibits NFkappaB and NFAT but not AP1 activity XREF_BIBR."
| 1
| 1

reach
"In contrast, AEB071 did not increase Annexin V positive cell populations or caspase-3 cleavage in UM cells harboring wild type GNAQ (XREF_FIG)."
Sotrastaurin affects ACE2 shedding D-glucose
| 1
Sotrastaurin inhibits ACE2 shedding D-glucose. 1 / 1
| 1

eidos
"On the other hand , sotrastaurin ( 10-5 M ) completely inhibited ACE2 shedding under conditions of high D-glucose ( 28 mM ) , to levels observed under basal conditions , with or without TAPI-1 ( Figure 2C ) ."
| 1

reach
"This approach was subsequently applied to measurement of the binding of axitinib, dabrafenib, erlotinib, gefitinib, ibrutinib, lapatinib, nilotinib, nintedanib, regorafenib, sorafenib, and trametinib to HLM (0.25 mg/ml)."
| 1

reach
"This approach was subsequently applied to measurement of the binding of axitinib, dabrafenib, erlotinib, gefitinib, ibrutinib, lapatinib, nilotinib, nintedanib, regorafenib, sorafenib, and trametinib to HLM (0.25 mg/ml)."
Recombinant hPXR affects dabrafenib
| 1
Dabrafenib binds recombinant hPXR. 1 / 1
| 1

reach
"We also showed that dabrafenib binds to recombinant hPXR, induces the expression of hPXR responsive genes in colon LS174T-hPXR cancer cells and human hepatocytes and finally increases the proliferation in LS174T-hPXR cells."
| 1

reach
"Pregabalin for the treatment of painful hand-foot skin reaction associated with dabrafenib."
| 1

reach
"In preclinical studies, there is strong evidence for the interaction of vemurafenib, dabrafenib, trametinib, palbociclib, cobimetinib and omipalisib with P-gp and BCRP."
| 1

reach
"This approach was subsequently applied to measurement of the binding of axitinib, dabrafenib, erlotinib, gefitinib, ibrutinib, lapatinib, nilotinib, nintedanib, regorafenib, sorafenib, and trametinib to HLM (0.25 mg/ml)."
| 1

reach
"This approach was subsequently applied to measurement of the binding of axitinib, dabrafenib, erlotinib, gefitinib, ibrutinib, lapatinib, nilotinib, nintedanib, regorafenib, sorafenib, and trametinib to HLM (0.25 mg/ml)."
Momelotinib affects viral yield
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Momelotinib inhibits viral yield. 1 / 1
| 1

eidos
"Thus , the reduction of viral yield by CYT387 was cooperatively enhanced when combined with tylophorine or DBQ 33b ( Fig. 4D-a ) ."

reach
"In the present study, it was demonstrated that momelotinib (MTB) enhanced the sensitivity of glioma cells to TMZ in vitro, as evidenced by a noticeable decrease in cell growth and a significant increase in apoptosis and autophagy following treatment with the combination of TMZ and MTB compared to TMZ alone."
Momelotinib affects signaling
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Momelotinib inhibits signaling. 1 / 1
| 1

sparser
"Similarly, inhibition of autocrine cytokine signaling by momelotinib in KRAS -dependent cells is associated with feedback induction of MEK/ERK signaling ( xref ), and combined inhibition of both STAT3 and ERK activation through the addition of selumetinib results in impressive synergy in the KP lung cancer GEMM [ xref ]."
Momelotinib affects responses post-ruxolitinib setting
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Momelotinib activates responses post-ruxolitinib setting. 1 / 1
| 1

eidos
"Fedratinib , pacritinib , and momelotinib can induce responses in the post-ruxolitinib setting ( Table2 ) ."

reach
"Citarinostat+ momelotinib triggers ROS generation and promotes ER stress."
Momelotinib affects protein IkappaBalpha phosphorylated
| 1
Momelotinib inhibits protein IkappaBalpha phosphorylated. 1 / 1
| 1

eidos
"Moreover , CYT387 diminished the protein level of IkappaBalpha and its phosphorylated form ( Fig. 2B-b ) , as did tylophorine ."
Momelotinib affects phosphorylation p65 TGEV infected ST cells
| 1
Momelotinib inhibits phosphorylation p65 TGEV infected ST cells. 1 / 1
| 1

eidos
"After a search of pathway pharmacological inhibitors for the additional effector pathways that mediate the phosphorylation of p65 , we found CYT387 , a JAK pathway inhibitor , diminished phosphorylation of p65 in TGEV infected ST cells ( Fig. 2B-b ) even in the presence of tylophorine ( Fig. 2B-c ) ."
Momelotinib affects malignant hematological cells
| 1
Momelotinib inhibits malignant hematological cells. 1 / 1
| 1

eidos
"( * p < 0.001 ) Citarinostat + momelotinib combination induced sub-G0 / G1 arrest in malignant hematological cells In WSU-NHL , Karpas-422 , RL , and Jeko-1 cells , citarinostat ( 4 muM ) alone induced a slight increase in the percentage of cells that entered the G0 / G1 phase , compared to untreated cells ."

reach
"Investigational agents include JAK inhibitors, such as ruxolitinib and momelotinib, or mTOR inhibitors including temsirolimus and everolimus."
Momelotinib affects induction IL-6
| 1
Momelotinib inhibits induction IL-6. 1 / 1
| 1

eidos
"As expected , IMD-0354 and CYT387 individually and significantly blocked the induction of IL-6 , a NF-kappaB target gene , in TGEV infected ST cells ( Fig. 2D ) ."
Momelotinib affects hepatic hepcidin
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Momelotinib inhibits hepatic hepcidin. 1 / 1
| 1

eidos
"6263 The mechanism behind this unexpected benefit of a JAK2 inhibitor was poorly understood until momelotinib was shown to down-regulate hepatic hepcidin production via antagonism of the type 1 activin receptor ( ACVR1 / ALK2 ) and ameliorate anemia in a rodent model of anemia of chronic disease ."
Momelotinib affects expression
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Momelotinib inhibits expression. 1 / 1
| 1

sparser
"Momelotinib (CYT387), a pharmacological inhibitor of IKBKE/TBK1, inhibits MYC expression, reduces viability and clonogenicity of primary AML cells, and demonstrates efficacy in a murine model of AML."

reach
"Citarinostat+ momelotinib triggers ROS generation and promotes ER stress."
Momelotinib affects dose dependent PSA AR mRNA protein LNCaP cells
| 1
Momelotinib inhibits dose dependent PSA AR mRNA protein LNCaP cells. 1 / 1
| 1

eidos
"Thirdly , CYT387 , which was developed as a JAK inhibitor but can also target IKBKE and TBK1 , resulted in a significant dose dependent reduction in PSA and AR mRNA and protein levels in LNCaP cells ( Figure 4D , E ) ."
Momelotinib affects bone morphogenic protein receptor kinase activin A receptor
| 1
Momelotinib activates bone morphogenic protein receptor kinase activin A receptor. 1 / 1
| 1

eidos
"Momelotinib is a JAK1 / 2 inhibitor , as well as directly inhibiting the bone morphogenic protein receptor kinase activin A receptor , type I ( ACVR1 ) - mediated expression of hepcidin.22This not only provides JAK inhibition , but also has a beneficial impact on anemia ."
Momelotinib affects activation
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Momelotinib inhibits activation. 1 / 1
| 1

sparser
"However, momelotinib effectively inhibited STAT3 activation suggesting that JAK-2 activation plays an important role in STAT3 activation in A549 cells."
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tas
No evidence text available
Momelotinib affects TBK1
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sparser
"The multi-targeted kinase inhibitor momelotinib inhibits both JAK1/2 and the TBK1 (and IKKe) kinases."
Momelotinib affects STING perinuclear foci parental Rab7-WT Rab7-S72A expressing MDA-MB-468 cells
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Momelotinib activates STING perinuclear foci parental Rab7-WT Rab7-S72A expressing MDA-MB-468 cells. 1 / 1
| 1

eidos
"Similarly , TBK1 / IKKepsilon inhibition with MRT67307 or CYT387 also resulted in the formation of STING perinuclear foci in parental , Rab7-WT , and Rab7-S72A expressing MDA-MB-468 cells , but not in Rab7-S72E cells ( Fig. 5A , 5C , and 5D ) ."
Momelotinib affects STAT1
| 1
Momelotinib leads to the phosphorylation of STAT1 on Y701. 1 / 1
| 1

reach
"Phosphorylation of STAT1 Y701 and STAT5 Y694 was inhibited by momelotinib and ruxolitinib."

reach
"Momelotinib also reduced BCR signaling, in contrast to ruxolitinib, indicating that these JAK inhibitors in fact have a distinct target spectrum."
Momelotinib affects Rab7-S72E cells
| 1
Momelotinib inhibits Rab7-S72E cells. 1 / 1
| 1

eidos
"Similarly , TBK1 / IKKepsilon inhibition with MRT67307 or CYT387 also resulted in the formation of STING perinuclear foci in parental , Rab7-WT , and Rab7-S72A expressing MDA-MB-468 cells , but not in Rab7-S72E cells ( Fig. 5A , 5C , and 5D ) ."
Momelotinib affects RIOK3
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tas
No evidence text available
Momelotinib affects Phosphorylation
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Momelotinib inhibits Phosphorylation. 1 / 1
| 1

sparser
"Phosphorylation of STAT1 Y701 and STAT5 Y694 was inhibited by momelotinib and ruxolitinib (Figure xref )."
| 1

eidos
"JAK2 inhibition either by CYT387 ( a JAK family inhibitor ) or by silencing JAK2-expression revealed a dominant JAK2 mediated p65 phosphorylation pathway for NF-kappaB activation and resulted in NF-kappaB inhibition , which overrode the IkappaBalpha regulation via the IKK-2 ."
Momelotinib affects MYLK4
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tas
No evidence text available
Momelotinib affects MYC
| 1
Momelotinib decreases the amount of MYC. 1 / 1
| 1

reach
"Momelotinib (CYT387), a pharmacological inhibitor of IKBKE and TBK1, inhibits MYC expression, reduces viability and clonogenicity of primary AML cells, and demonstrates efficacy in a murine model of AML."
Momelotinib affects IGF1R
| 1
Momelotinib leads to the phosphorylation of IGF1R. 1 / 1
| 1

reach
"In A549 cells, momelotinib treatment for 24 hr increased phosphorylation of IGF1 receptor (IGF1R), in contrast to the JAK1/2 specific inhibitor ruxolitinib."
Momelotinib affects IGF1
| 1
Momelotinib leads to the phosphorylation of IGF1. 1 / 1
| 1

reach
"In A549 cells, momelotinib treatment for 24 hr increased phosphorylation of IGF1 receptor (IGF1R), in contrast to the JAK1/2 specific inhibitor ruxolitinib."
Momelotinib affects IGF1 receptor
| 1
Momelotinib leads to the phosphorylation of IGF1 receptor. 1 / 1
| 1

reach
"In A549 cells, momelotinib treatment for 24 hr increased phosphorylation of IGF1 receptor (IGF1R), in contrast to the JAK1/2 specific inhibitor ruxolitinib."
Momelotinib affects IC 50 18 nm
| 1
Momelotinib inhibits IC 50 18 nm. 1 / 1
| 1

reach
"28 Finally, momelotinib (also known as CYT-387) inhibits both JAK1 (IC 50 11 nm) and JAK2 (IC 50 18 nm), rather than JAK3 (IC 50 0.16 muM), although off-target effects (serine/threonine kinase IKBKE) have been described."
Momelotinib affects IC 50 11 nm
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Momelotinib inhibits IC 50 11 nm. 1 / 1
| 1

reach
"28 Finally, momelotinib (also known as CYT-387) inhibits both JAK1 (IC 50 11 nm) and JAK2 (IC 50 18 nm), rather than JAK3 (IC 50 0.16 muM), although off-target effects (serine/threonine kinase IKBKE) have been described."
Momelotinib affects IC 50 0.16 muM
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Momelotinib inhibits IC 50 0.16 muM. 1 / 1
| 1

reach
"28 Finally, momelotinib (also known as CYT-387) inhibits both JAK1 (IC 50 11 nm) and JAK2 (IC 50 18 nm), rather than JAK3 (IC 50 0.16 muM), although off-target effects (serine/threonine kinase IKBKE) have been described."
Momelotinib affects HAMP
| 1
| 1

reach
"Momelotinib inhibits ACVR1 and ALK2, decreases hepcidin production, and ameliorates anemia of chronic disease in rodents."
Momelotinib affects ERK
| 1
| 1

reach
"Notably, momelotinib induced a robust dose dependent activation of ERKs signaling in a heterogeneous panel of cancer cells regardless of (HER3) activation."
Momelotinib affects CHUK
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tas
No evidence text available
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tas
No evidence text available
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tas
No evidence text available
Lestaurtinib affects virus yield
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Lestaurtinib inhibits virus yield. 1 / 1
| 1

eidos
"Fig. 5 : Chaetocin , gemcitabine and lestaurtinib reduce virus yield from infected cells ."
| PMC
Lestaurtinib affects virus yield infected cells.A549 cells
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Lestaurtinib inhibits virus yield infected cells.A549 cells. 1 / 1
| 1

eidos
"Chaetocin , gemcitabine and lestaurtinib reduce virus yield from infected cells.A549 cells were infected at an MOI of 10 of HAdV for 1 h , and washed with PBS to remove unbound virus before adding medium containing vehicle or compound ( chaetocin at 1 muM , gemcitabine at 0.5 muM and lestaurtinib at 5 muM ) ."
| PMC
Lestaurtinib affects pro-inflammatory transcription NFkappaB
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Lestaurtinib inhibits pro-inflammatory transcription NFkappaB. 1 / 1
| 1

eidos
"The pro-inflammatory transcription factor NFkappaB is inhibited by fluoro-and tribromsalans , sunitinib , lestaurtinib , ectinascidin , chromomycin and bortezomib [ 720 ] ."
Lestaurtinib affects penton HAdV
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Lestaurtinib inhibits penton HAdV. 1 / 1
| 1

eidos
"Both chaetocin and lestaurtinib effectively abrogated penton expression from both HAdV at the 24 h timepoint , while gemcitabine reduced penton protein levels to ~ 5 % of that observed in vehicle-treated cells at 24 hpi ."
| PMC
Lestaurtinib affects outcome
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Lestaurtinib activates outcome. 1 / 1
| 1

eidos
"For example , in a randomized study of lestaurtinib administered in sequence with intensive chemotherapy for FLT3-mutated AML , the addition of lestaurtinib did not lead to an improved outcome ( Levis et al ., 2011 ) ."
Lestaurtinib affects late Figure HAdV-5
| 1
Lestaurtinib inhibits late Figure HAdV-5. 1 / 1
| 1

eidos
"As chaetocin , gemcitabine and lestaurtinib all decreased genome copy numbers ( Figure 4 ) and late gene expression ( Figure 3 ) of HAdV-5 at 24 hpi , we predicted that these compounds would also affect yield of virus from the infected cells ."
| PMC
Lestaurtinib affects infected vehicle-treated cells
| 1
Lestaurtinib activates infected vehicle-treated cells. 1 / 1
| 1

eidos
"Chaetocin and lestaurtinib led to a 2-log reduction in genome copy number within the treated cells at 24 hpi , relative to infected , vehicle-treated cells ."
| PMC
Lestaurtinib affects genome copy
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Lestaurtinib inhibits genome copy. 1 / 1
| 1

eidos
"As chaetocin , gemcitabine and lestaurtinib all decreased genome copy numbers ( Figure 4 ) and late gene expression ( Figure 3 ) of HAdV-5 at 24 hpi , we predicted that these compounds would also affect yield of virus from the infected cells ."
| PMC
Lestaurtinib affects genome copy Fig. late Fig. HAdV-5
| 1
Lestaurtinib inhibits genome copy Fig. late Fig. HAdV-5. 1 / 1
| 1

eidos
"As chaetocin , gemcitabine and lestaurtinib all decreased genome copy numbers ( Fig. 4 ) and late gene expression ( Fig. 3 ) of HAdV-5 at 24 hpi , we predicted that these compounds would also affect yield of virus from the infected cells ."
| PMC

ctd
No evidence text available
Lestaurtinib affects JAK2
| 1
Lestaurtinib inhibits JAK2. 1 / 1
| 1

medscan
"One of these inhibitors is lestaurtinib, which inhibits JAK2 with an IC50 of about 1 nM ( )."
Lestaurtinib affects FLT3
| 1
Lestaurtinib inhibits FLT3. 1 / 1
| 1

medscan
"Because we noted that in vivo FLT3 inhibition by lestaurtinib was less effective in the relapsed patients compared with the newly diagnosed patients, we investigated whether plasma FLT3 ligand levels could influence the efficacy of FLT3 inhibition in these patients."
Lestaurtinib affects 2-log genome copy treated cells hpi
| 1
Lestaurtinib inhibits 2-log genome copy treated cells hpi. 1 / 1
| 1

eidos
"Chaetocin and lestaurtinib led to a 2-log reduction in genome copy number within the treated cells at 24 hpi , relative to infected , vehicle-treated cells ."
| PMC
Lestaurtinib affects % muM
| 1
Lestaurtinib inhibits % muM. 1 / 1
| 1

eidos
"At 5 muM , chaetocin induced a 40 % reduction in metabolic activity in treated cells , while gemcitabine had no noticeable impact , and lestaurtinib led to only a 25 % reduction at 10 muM ."
| PMC
| 1

reach
"This approach was subsequently applied to measurement of the binding of axitinib, dabrafenib, erlotinib, gefitinib, ibrutinib, lapatinib, nilotinib, nintedanib, regorafenib, sorafenib, and trametinib to HLM (0.25 mg/ml)."
| 1

reach
"This approach was subsequently applied to measurement of the binding of axitinib, dabrafenib, erlotinib, gefitinib, ibrutinib, lapatinib, nilotinib, nintedanib, regorafenib, sorafenib, and trametinib to HLM (0.25 mg/ml)."
| 1

reach
"This approach was subsequently applied to measurement of the binding of axitinib, dabrafenib, erlotinib, gefitinib, ibrutinib, lapatinib, nilotinib, nintedanib, regorafenib, sorafenib, and trametinib to HLM (0.25 mg/ml)."
| 1

reach
"This approach was subsequently applied to measurement of the binding of axitinib, dabrafenib, erlotinib, gefitinib, ibrutinib, lapatinib, nilotinib, nintedanib, regorafenib, sorafenib, and trametinib to HLM (0.25 mg/ml)."
Dabrafenib bound to BRAF activates signal transduction. 1 / 1
| 1

reach
"The small molecule inhibitors vemurafenib and dabrafenib selectively bind the active conformation of BRAF and inhibit signal transduction between BRAF and MEK."
Dabrafenib affects robust apoptosis cancer cells harboring BRAF V600E TERT mutations
| 1
Dabrafenib activates robust apoptosis cancer cells harboring BRAF V600E TERT mutations. 1 / 1
| 1

eidos
"Using thyroid cancer , melanoma , and colon cancer cell models , we showed that dabrafenib and trametinib induced robust apoptosis of cancer cells harboring both BRAF V600E and TERT promoter mutations but had little proapoptotic effect in cells harboring only BRAF V600E ."

reach
"Based on the fact that dabrafenib induces ER stress response in melanoma cells, we then tried to determine whether ER stress induced by dabrafenib will protect the cancer cells from the cytotoxicity of the drug."

reach
"Moreover, dabrafenib rather than another clinically used B-Raf inhibitor vemurafenib (with poor RIP3 inhibitory activity) reversed the loss of propidium iodide (PI)-negative HT29 cells caused by TSZ (XREF_SUPPLEMENTARY)."
Dabrafenib affects patient survival
| 1
Dabrafenib activates patient survival. 1 / 1
| 1

medscan
"The selective BRAF inhibitors vemurafenib and dabrafenib have shown significant improvement in patient survival compared with standard therapy in BRAF V600-mutant metastatic melanoma. 44999999="V600"}"
| 1

reach
"In addition, z-VAD increased cell death induced by acetaminophen, which was prevented by dabrafenib partly (XREF_SUPPLEMENTARY); dabrafenib but not vemurafenib decreased the acetaminophen induced loss of the cell viability (XREF_SUPPLEMENTARY)."
Dabrafenib affects overall survival
| 1
Dabrafenib activates overall survival. 1 / 1
| 1

medscan
"Loss of p14ARF permits unregulated cell division while loss of p16INK4a leads to dysregulation of p53 and pervasive genetic instability. , In patients with late-stage BRAFV600E melanomas, BRAF inhibitors (for example, dabrafenib or vemurafenib) confer a survival advantage when compared with chemotherapy, demonstrating improvements in response-rates, progression-free survival and overall survival. , Initial responses to BRAF inhibitors are not durable, and patient relapse usually occurs within 6-7 months. , The use of concurrent BRAF and MEK inhibitors (for example, cobimetinib, selumetinib or trametinib) for patients with melanoma has been established as a synergistic treatment approach and one that has further improved response compared with BRAF monotherapy."
Dabrafenib affects nuclear factor-kappaB
| 1
Dabrafenib inhibits nuclear factor-kappaB. 1 / 1
| 1

reach
"Dabrafenib suppressed the PolyP mediated vascular barrier permeability, upregulation of inflammatory biomarkers, adhesion and migration of leukocytes, and activation and/or production of nuclear factor-kappaB, tumor necrosis factor-alpha, and interleukin-6."
Dabrafenib affects mek
| 1
Dabrafenib activates mek. 1 / 1
| 1

reach
"In addition, in normal cells, vemurafenib and dabrafenib can activate mek signaling through upstream activation of craf, which is the cause of the secondary squamous cell skin carcinomas observed in patients treated with these agents."
Dabrafenib affects liver injury
| 1
Dabrafenib inhibits liver injury. 1 / 1
| 1

medscan
"The B-Raf(V600E) inhibitor dabrafenib selectively inhibits RIP3 and alleviates acetaminophen-induced liver injury. 46999999="V600E"}"

reach
"The combined dabrafenib and trametinib treatment led to a prominent immune response with foamy macrophages engorging the fibrovascular cores and CD8 positive T cells infiltrating throughout the tumor."
| 1

reach
"In patients with CNS metastases treated with dabrafenib, extra- and intracranial PFS was similar and there was little difference seen in efficacy between extra- and intracranial sites, but number of patients was limited (n = 23) and the analysis did not discriminate between sites of extracranial metastasis or the possibility that there was a larger initial number of extracranial metastases (Azer etal., 2014)."
| 1
Dabrafenib decreases the amount of glucose. 1 / 1
| 1

reach
"Compared to BRAF wild-type BHP 2-7 cells, BRAF inhibitor dabrafenib preferentially inhibited ERK signaling and thyroid cancer cell proliferation, arrested cell circle, and regulated iodine and glucose handling gene expression in BRAF V600E -positive PTC cells."
| 1

reach
"Pre-treatment of pancreatic cancer and non small cell lung cancer cell lines with sublethal doses of 50nM and 5nM of gemcitabine respectively, enhanced killing by both vemurafenib and dabrafenib."
Dabrafenib affects extracellular signal-related kinase
| 1
Dabrafenib activates extracellular signal-related kinase. 1 / 1
| 1

reach
"XREF_BIBR, XREF_BIBR The combination of dabrafenib and trametinib, targeting mitogen activated extracellular signal related kinase (MEK) which is downstream of BRAF in the MAPK pathway, was also approved by US FDA in 2014 based on increased PFS and OS over single dabrafenib or vemurafenib monotherapy."

reach
"Among the drugs tested, only epirubicin hydrochloride and dabrafenib mesylate exhibited> 50% cis-inhibitory effect, in COS-7 cells, on hOAT4 mediated uptake of estrone sulfate, a prototypical substrate for the transporter."
Dabrafenib affects ear
| 1
| 1

reach
"In passive cutaneous anaphylaxis, oral administration of dabrafenib (0.1, 1, 10mg/kg) reduced local pigmentation and ear thickness in a dose dependent manner."
Dabrafenib affects cutaneous squamous-cell carcinoma
| 1
Dabrafenib activates cutaneous squamous-cell carcinoma. 1 / 1
| 1

medscan
"However, dabrafenib produces a little weaker clinical therapeutic effect and causes lower incidence of cutaneous squamous-cell carcinoma (incidence: 6% in a dabrafenib phase III trial versus 26% in a vemurafenib phase III trial), a common side effect of B-RafV600E inhibitors."
Dabrafenib affects cutaneous squamous cell carcinoma
| 1
Dabrafenib activates cutaneous squamous cell carcinoma. 1 / 1
| 1

medscan
"Monotherapy with vemurafenib, dabrafenib, and encorafenib induces neoplasia, most often cutaneous squamous cell carcinoma , at rates of approximately 22%, 6%, and 3.7%, respectively [ , - ], averaged across multiple phase I-III trials conducted in heterogeneous patient populations."
Dabrafenib affects cuSCC/KA
| 1
Dabrafenib inhibits cuSCC/KA. 1 / 1
| 1

reach
"Indeed, a second clinical grade RAF inhibitor, dabrafenib, effectively inhibits mutant BRAF signaling, elicits strong clinical responses in patients but also induces the formation of cuSCC/KA."
Dabrafenib affects complete response
| 1
Dabrafenib activates complete response. 1 / 1
| 1

medscan
"The concurrent administration of dabrafenib and trametinib was associated with a higher incidence of complete response (9% vs. 4%) and longer progression-free survival (9.4 months vs. 5.8 months) compared to dabrafenib alone."
Dabrafenib affects cerium
| 1
| 1

reach
"We found several compounds that could rescue phenotypes in KS zebrafish models; however, our most promising result is desmethyl Dabrafenib (dmDf), a soluble BRAF inhibitor that rescues not only the CE defects of KS morphant and mutant zebrafish embryos, but also the craniofacial and neuroanatomical defects of kmt2d-, rap1- and kdm6a depleted zebrafish larvae, across both transient and stable genetic models."
Dabrafenib affects cell
| 1
| 1

eidos
"Interestingly , the inhibition of JNK2 effects in the cell lines appears to be somewhat different in that the maximum effect of dabrafenib is augmented in m229R cells and the IC50 is decreased in SK-MEL28R cells ( Supplementary Table 2 ) ."

reach
"Dabrafenib and Vemurafenib treatments for 24 h markedly reduced cell migration compared to the untreated cells (scratch was completely closed) (XREF_FIG)."

reach
"Dabrafenib suppressed the PolyP mediated vascular barrier permeability, upregulation of inflammatory biomarkers, adhesion and migration of leukocytes, and activation and/or production of nuclear factor-kappaB, tumor necrosis factor-alpha, and interleukin-6."
| 1

reach
"This approach was subsequently applied to measurement of the binding of axitinib, dabrafenib, erlotinib, gefitinib, ibrutinib, lapatinib, nilotinib, nintedanib, regorafenib, sorafenib, and trametinib to HLM (0.25 mg/ml)."
Dabrafenib affects anti-BRAF
| 1
Dabrafenib inhibits anti-BRAF-V600E. 1 / 1
| 1

reach
"Although anti-BRAF V600E inhibitors including vemurafenib (PLX4032) and dabrafenib were approved in treating melanoma patients harboring this mutation, drug resistance is frequently reported, suggesting a limitation of single agent treatment."
Dabrafenib affects WMD1
| 1
Dabrafenib activates WMD1. 1 / 1
| 1

reach
"Patient WMD1 from Australia was treated with dabrafenib for 5 years, and on surveillance 18-fluorodeoxy (FDG) positron emission tomography and computed tomography (PET/CT) scan (XREF_FIG), an FDG avid lesion in the transverse colon was found and interpreted as a potential melanoma metastases."
Dabrafenib affects VEGFA
| 1
| 1

reach
"A375 and A375R cells differently responded to dabrafenib, which strongly inhibited invasiveness and VEGF-A secretion in A375 cells, whereas it stimulated these functions in A375R cells."
| PMC
Dabrafenib affects VEGF
| 1
| 1

reach
"Interestingly, we also observed decreased VEGF expression by microarray in the tumors treated with dabrafenib."
Dabrafenib affects UGT1A1
| 1
| 1

reach
"Dabrafenib, ibrutinib, nintedanib and trametinib were potent inhibitors of human liver microsomal UGT1A1; K i, u values ranged from 1.1 to 7.5 microM."

eidos
"Dabrafenib , as an inhibitor of RIPK3 , may be an effective treatment to limit the progression of the tubulointerstitial fibrosis ."
Dabrafenib affects TYRP1
| 1
| 1

reach
"Similar trend was observed when TYRP1 transcript level was analyzed in samples from patients treated with a combination of dabrafenib and trametinib."
Dabrafenib affects TSHR
| 1
| 1

medscan
"Western blot analysis demonstrated that dabrafenib restored the expression of NIS, thyroglobulin, TSHR, and thyroperoxidase, and reduced the expression of GLUT1 (Figure ) in both BCPAP and K1 cells."
Dabrafenib affects TPO
| 1
| 1

medscan
"Western blot analysis demonstrated that dabrafenib restored the expression of NIS, thyroglobulin, TSHR, and thyroperoxidase, and reduced the expression of GLUT1 (Figure ) in both BCPAP and K1 cells."
Dabrafenib affects TGFBR1
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1 |

tas
No evidence text available
Dabrafenib affects TGFBI
1 |
Dabrafenib increases the amount of TGFBI. 1 / 1
1 |

ctd
No evidence text available
Dabrafenib affects TG
| 1
Dabrafenib activates TG. 1 / 1
| 1

medscan
"Western blot analysis demonstrated that dabrafenib restored the expression of NIS, thyroglobulin, TSHR, and thyroperoxidase, and reduced the expression of GLUT1 (Figure ) in both BCPAP and K1 cells."
Dabrafenib affects TESK1
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1 |

tas
No evidence text available
Dabrafenib affects TERT
| 1
| 1

reach
"Using thyroid cancer, melanoma, and colon cancer cell models, we showed that dabrafenib and trametinib induced robust apoptosis of cancer cells harboring both BRAF V600E and TERT promoter mutations but had little proapoptotic effect in cells harboring only BRAF V600E."

medscan
"To date, two popular second-generation BRAF inhibitors, dabrafenib and vemurafenib, have shown the promising efficacy in patients with BRAF V600E-mutant non-small-cell lung cancer. 46999999="V600E"}"
Dabrafenib affects SRMS
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1 |

tas
No evidence text available
Dabrafenib affects SLC2A3
| 1
| 1

reach
"Importantly, expression of GLUT1, GLUT3 or HK2 mRNA was suppressed in melanoma biopsies from patients treated with the BRAFi dabrafenib or vemurafenib and, in some cases, was restored after disease progression."
Dabrafenib affects SLC2A1
| 1
Dabrafenib decreases the amount of SLC2A1. 1 / 1
| 1

reach
"Western blot analysis demonstrated that dabrafenib restored the expression of NIS, Tg, TSHR, and TPO, and reduced the expression of GLUT1 in both BCPAP and K1 cells."
Dabrafenib affects RELA
1 |
1 |

ctd
No evidence text available
Dabrafenib affects RAS-RAF-MEK-ERK
| 1
Dabrafenib inhibits RAS-RAF-MEK-ERK. 1 / 1
| 1

reach
"Taken together, these results suggest that TAS-116 enhances apoptosis induced by RAS-RAF-MEK-ERK pathway inhibitors including dabrafenib via mitochondrial damage in MM cells."
Dabrafenib affects RAS
| 1
| 1

reach
"Because HSP90 inhibitors block multiple pathways crucial to MM survival [XREF_BIBR, XREF_BIBR, XREF_BIBR], the combination of TAS-116 and dabrafenib enhances the anti-MM effect in RAS mutated and wild-type BRAF MM cells via a mechanism other than ERK pathway inhibition."
Dabrafenib affects RAF/MEK/ERK
| 1
Dabrafenib inhibits RAF/MEK/ERK. 1 / 1
| 1

reach
"Recently, RAF/MEK/ERK pathway inhibitors, including the BRAF inhibitors (BRAFi) vemurafenib (RG7204; PLX4032) and dabrafenib (GSK2118436), have been validated for treatment of BRAF V600 melanoma, with striking response rates in excess of 50% in patients diagnosed with BRAF V600 metastatic melanoma."
Dabrafenib affects RAC1
| 1
Dabrafenib activates RAC1-P29S. 1 / 1
| 1

reach
"We next examined the apoptotic response to RAF inhibition in our isogenic cell lines by immunoblotting for cleaved-PARP in lysates from GFP and RAC1 P29S overexpressing A375 and 451Lu cells treated with dabrafenib."
Dabrafenib affects PTPN11
| 1
| 1

reach
"However, the triple combination dabrafenib, trametinib, and SHP099 markedly suppressed p (Y542) SHP2 (XREF_FIG) and ERK signaling (XREF_FIG) and growth (XREF_FIG) of RKO xenograft tumors, without any obvious effect on body weight (XREF_SUPPLEMENTARY), providing further evidence that combined ERK signaling and SHP2 inhibition may be an effective therapeutic strategy for patients with BRAF (V600E) colorectal tumors."
| 1
| 1

reach
"Selumetinib (a selective MEK inhibitor) and dabrafenib (a selective BRAF inhibitor used in BRAF mutated tumors) have been shown to increase RAI uptake by RAI-refractory tumor tissues XREF_BIBR, XREF_BIBR, and these encouraging results are now under investigation (NCT02393690 and NCT03244956)."
Dabrafenib affects PPARG
| 1

reach
"Moreover, PPARgamma and dabrafenib complex shows high RMSF value for Met252, Gln279, Phe360, and Glu460."
Dabrafenib affects PLK4
1 |
1 |

tas
No evidence text available
1 |
1 |

tas
No evidence text available
Dabrafenib affects PGR
| 1
| 1

reach
"While the combination of dabrafenib and trametinib caused a PR of the patient 's melanoma, at 12 weeks the patient presented with a brain metastasis that, upon resection, was characterized as originating from a KRAS mutated colon cancer."
Dabrafenib affects PERK12
| 1
| 1

reach
"Lapatinib blocked the superactivated HER2 and HER3, AKT and pERK1/2 induced by dabrafenib."
Dabrafenib affects PDCD1
| 1
| 1

reach
"Additional compounds and antibodies for targeted, immuno- as well as combination therapy have been and are currently being developed such as the BRAF V600mut inhibitor dabrafenib [XREF_BIBR], mitogen activated protein kinase kinase (MEK) inhibitors trametinib [XREF_BIBR] and cobimetinib [XREF_BIBR], the anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody ipilimumab [XREF_BIBR] as well as anti-programmed cell death protein 1 (PD-1) antibodies pembrolizumab [XREF_BIBR] and nivolumab [XREF_BIBR]."
Dabrafenib affects NT5E
| 1
| 1

medscan
"In addition, dabrafenib and trametinib treatment of CD73+BRAFV600E-mutant melanomas caused profound CD73 downregulation in tumor cells."
Dabrafenib affects NSP9
| 1
| 1

reach
"Dabrafenib, a medication for the treatment of BRAF-associated cancers, is predicted to inhibit NEK9, an interactor of NSP9."
Dabrafenib affects NR1I3
| 1
| 1

reach
"In that context, the potential of the anticancer BRAF inhibitor dabrafenib suspected to activate hPXR and the human constitutive androstane receptor (hCAR) has not been thoroughly investigated yet."
Dabrafenib affects NR1I2
| 1
| 1

reach
"The Anti-Cancer Drug Dabrafenib Is a Potent Activator of the Human Pregnane X Receptor."
Dabrafenib affects NGFR
| 1
| 1

reach
"In the case of BET inhibitor JQ1, we also show that co-drugging suppresses the NGFR High state in BRAF-mutant melanoma xenografts treated with dabrafenib."
Dabrafenib affects NFE2L2
| 1
| 1

eidos
"Combination of diABZI and BRAF Inhibitors Activate STING and Prevent NRF2 Translocation Since we observed that diABZI potently activates STING pathway and prevents NRF2 activation , we investigated if the combination of diABZi with the currently available BRAFis ; Dabrafenib and Vemurafenib will also activate STING and inhibit NRF2 ."
Dabrafenib affects MMP9
| 1
| 1

reach
"In both siCTRL and A375R and siPTTG1 and A375R cells, exposure to dabrafenib increased MMP-9 secretion."
Dabrafenib affects MAPK3
1 |
Dabrafenib phosphorylates MAPK3. 1 / 1
1 |

ctd
No evidence text available
Dabrafenib affects MAPK1
1 |
Dabrafenib phosphorylates MAPK1. 1 / 1
1 |

ctd
No evidence text available
Dabrafenib affects MAP4K5
| 1
| 1

reach
"Neither MKK4 nor MAP4K5 is substantially inhibited by dabrafenib up to 1 muM (XREF_FIG)."
Dabrafenib affects MAP2K4
| 1
| 1

reach
"Neither MKK4 nor MAP4K5 is substantially inhibited by dabrafenib up to 1 muM (XREF_FIG)."
Dabrafenib affects MAP2K2
| 1
| 1

reach
"Finally, dabrafenib and trametinib are small molecule inhibitors of BRAF and MEK1 and MEK2, respectively."
Dabrafenib affects MAP2K
| 1
| 1

reach
"Inhibitors of mutated rapidly accelerated fibrosarcoma kinase B (BRAF), e.g., dabrafenib and vemurafenib, and inhibitors of mitogen-activated protein kinase kinase (MEK), e.g., trametinib and cobimetinib, are used for melanoma therapy."
| 1
| 1

reach
"Dabrafenib does not rescue a zebrafish model of KS."

medscan
"Two BRAF inhibitors, vemurafenib and dabrafenib, have shown clinical activity in metastatic BRAFV600E mutant lung cancers [ , , ]."
Dabrafenib affects LIMK2
1 |
1 |

tas
No evidence text available
Dabrafenib affects KRAS
| 1
| 1

reach
"Interestingly, dabrafenib increased NRAS and KRAS in NCI-H929 cells, and NRAS in RPMI-8226 cells."
Dabrafenib affects KIT
| 1
Dabrafenib decreases the amount of KIT. 1 / 1
| 1

reach
"The combination of a BRAF inhibitor (dabrafenib) and a MEK inhibitor (trametinib) increases the expression of KIT, a tumor suppressor, and also induces alterations in CCND1, RB1, and MET in patients with BRAF V600E metastatic melanoma."
Dabrafenib affects KDR
| 1
Dabrafenib decreases the amount of KDR. 1 / 1
| 1

reach
"Dabrafenib reduced invasiveness, VEGFR-2 expression and VEGF-A secretion in A375 cells, whereas it increased invasiveness, VEGF-A and MMP-9 release in A375R cells."
| 1

reach
"As a serine threonine kinase, which consumes ATP as an energy source, BRAF makes it a target for ATP competitive inhibitors such as small molecular; being the most developed, vemurafenib, dabrafenib, and trametinib in the future may play an important role in the adjuvant setting, either alone or associated with chemotherapy or interferon."
Dabrafenib affects ITGB5
1 |
Dabrafenib increases the amount of ITGB5. 1 / 1
1 |

ctd
No evidence text available
Dabrafenib affects ITGAV
1 |
Dabrafenib increases the amount of ITGAV. 1 / 1
1 |

ctd
No evidence text available
Dabrafenib affects IRF3
| 1
Dabrafenib leads to the phosphorylation of IRF3. 1 / 1
| 1

reach
"As speculated, combined treatment of Dabrafenib or Vemurafenib with diABZI, enhanced phosphorylation of STING (XREF_FIG) and IRF3 (XREF_FIG)."
Dabrafenib affects IL6
| 1
| 1

reach
"Dabrafenib suppressed the PolyP mediated vascular barrier permeability, upregulation of inflammatory biomarkers, adhesion and migration of leukocytes, and activation and/or production of nuclear factor-kappaB, tumor necrosis factor-alpha, and interleukin-6."
Dabrafenib affects HR
| 1
Dabrafenib activates HR. 1 / 1
| 1

reach
"In two randomized phase III trials, the combination of dabrafenib plus trametinib significantly prolonged progression-free survival (PFS) and OS compared with either vemurafenib monotherapy (PFS : HR, 0.61; p <.001; and OS : HR, 0.66; p <.001) or dabrafenib plus placebo (PFS : HR, 0.67; p =.0004; and OS : HR, 0.71; p =.0107) in patients with previously untreated, unresectable BRAF V600-mutant melanoma [14], [38]."
Dabrafenib affects HK2
| 1
| 1

reach
"Importantly, expression of GLUT1, GLUT3 or HK2 mRNA was suppressed in melanoma biopsies from patients treated with the BRAFi dabrafenib or vemurafenib and, in some cases, was restored after disease progression."
Dabrafenib affects GPT
1 |
Dabrafenib increases the amount of GPT. 1 / 1
1 |

ctd
No evidence text available
Dabrafenib affects GLUT1
| 1
Dabrafenib activates GLUT1. 1 / 1
| 1

medscan
"Western blot analysis demonstrated that dabrafenib restored the expression of NIS, thyroglobulin, TSHR, and thyroperoxidase, and reduced the expression of GLUT1 (Figure ) in both BCPAP and K1 cells."
Dabrafenib affects GIST case
| 1
Dabrafenib activates GIST case. 1 / 1
| 1

reach
"Falchook et al. recently reported a GIST case effectively treated with Dabrafenib [XREF_BIBR]."
Dabrafenib affects F3
| 1
| 1

reach
"Dabrafenib and Trametinibcaused the down-regulation of TF in both cell lines A-375 and SK-MEL-28."
Dabrafenib affects ERBB3
| 1
| 1

reach
"Lapatinib blocked the superactivated HER2 and HER3, AKT and pERK1/2 induced by dabrafenib."
| 1
| 1

eidos
"The model was an extension of the model of PC-12 ( rat adrenal gland ) cells [ 47 ] and showed that increasing dabrafenib concentrations cause declining pERK levels but in unphysiological ranges ."
Dabrafenib affects EGFR inhibitors
| 1
Dabrafenib activates EGFR inhibitors. 1 / 1
| 1

reach
"These early data led to several dual combination trials involving BRAF inhibitors, such as vemurafenib or dabrafenib, and the EGFR inhibitors cetuximab or panitumumab, respectively."
Dabrafenib affects E2F4
| 1
Dabrafenib increases the amount of E2F4. 1 / 1
| 1

reach
"We first assessed the effect of PLX4032 on E2F1 and E2F4 levels and we observed that BRAF inhibitors, PLX4032 and dabrafenib, reduce E2F1 and E2F4 levels."
Dabrafenib affects E2F1
| 1
Dabrafenib increases the amount of E2F1. 1 / 1
| 1

reach
"We first assessed the effect of PLX4032 on E2F1 and E2F4 levels and we observed that BRAF inhibitors, PLX4032 and dabrafenib, reduce E2F1 and E2F4 levels."
| 1

reach
"We also elucidate a novel dabrafenib induced DNA repair delay following MTX induced single strand DNA (ssDNA) breaks."
Dabrafenib affects D-dimer
| 1
Dabrafenib increases the amount of D-dimer. 1 / 1
| 1

reach
"Sudden elevation of plasma D-dimer levels induced by the combination therapy of dabrafenib and trametinib : Report of two cases."
Dabrafenib affects Counting Kit-8
| 1
Dabrafenib activates Counting Kit-8. 1 / 1
| 1

reach
"We harvested and examined cell viability by the Cell Counting Kit-8 and found that the group treated with only dabrafenib was more resistant to the drug in comparison to the group that was cotreated with 4-phenylbutyrate."
Dabrafenib affects CSK
1 |
1 |

tas
No evidence text available
Dabrafenib affects CSF3
| 1
| 1

reach
"Granulocyte colony stimulating factor producing melanoma treated with the combination of dabrafenib and trametinib."
Dabrafenib affects CRC
| 1
| 1

reach
"We previously reported a patient with synchronous BRAF mutated metastatic melanoma and BRAF wt / KRAS G12D -metastatic colorectal cancer (CRC), whose CRC relapsed and progressed when treated with the BRAF inhibitor dabrafenib (GSK2118436)."
Dabrafenib affects CRAF-CRY2
| 1
Dabrafenib increases the amount of CRAF-CRY2. 1 / 1
| 1

reach
"Interestingly, dabrafenib seems to significantly enhance the protein levels of CRAF-CRY2."
Dabrafenib affects CRAF-CIBN
| 1
Dabrafenib increases the amount of CRAF-CIBN. 1 / 1
| 1

reach
"Already at a concentration of 1muM, dabrafenib elevated the protein level of the light-insensitive constructs CRAF and CRAF-CIBN, higher concentrations tested up to 10muM further increased their protein level (XREF_FIG)."
Dabrafenib affects CRAF-CIBN fusion proteins
| 1
Dabrafenib increases the amount of CRAF-CIBN fusion proteins. 1 / 1
| 1

reach
"Dabrafenib elevated the protein levels of CRAF-CRY2 and CRAF-CIBN fusion proteins in cells, an effect independent of light exposure (XREF_FIG C, XREF_FIG A, C)."
Dabrafenib affects COQ8B
1 |
1 |

tas
No evidence text available
Dabrafenib affects COQ8A
1 |
1 |

tas
No evidence text available
Dabrafenib affects CHEK1
| 1
| 1

reach
"In cell based studies of NRAS- and KRAS-mutant cancer cells, dabrafenib inhibited the NEK9 target CHK1, whereas vemurafenib did not."
Dabrafenib affects CDKN1B
| 1
| 1

reach
"In a BRAF (V600E)-containing xenograft model of human melanoma, orally administered dabrafenib inhibited ERK activation, downregulated Ki67, and upregulated p27, leading to tumor growth inhibition."
Dabrafenib affects CDK18
1 |
1 |

tas
No evidence text available
Dabrafenib affects CDK17
1 |
1 |

tas
No evidence text available
Dabrafenib affects CD8
| 1
| 1

reach
"Of note, dabrafenib and trametinib without anti-PD-1 also significantly increased CD3 + CD8 + cells in the tumors compared to vehicle, whereas a non significant trend toward an increase in CD3 + CD8 + cells was observed with anti-PD-1, dabrafenib and anti-PD-1 or trametinib and anti-PD-1."
Dabrafenib affects CD3
| 1
| 1

reach
"Of note, dabrafenib and trametinib without anti-PD-1 also significantly increased CD3 + CD8 + cells in the tumors compared to vehicle, whereas a non significant trend toward an increase in CD3 + CD8 + cells was observed with anti-PD-1, dabrafenib and anti-PD-1 or trametinib and anti-PD-1."
Dabrafenib affects CCND1
| 1
| 1

reach
"Increased cyclin D expression mediates inherent resistance to mutant BRAF inhibition [XREF_BIBR], and copy number changes in CDKN2A, CCND1 correlated with the shortened duration of PFS in patients treated with dabrafenib [XREF_BIBR]."
Dabrafenib affects CASP3
| 1
| 1

reach
"PARP1 and caspase 3 cleavage patterns in SK-MEL-28VR1 cells treated with MTX + dabrafenib (lanes 12-15) indicated that caspase 3 is cleaved and activated by 24 hours after combination treatments (lane 12), but PARP1 is not cleaved at that time point."
Dabrafenib affects BREAK trials
| 1
Dabrafenib activates BREAK trials. 1 / 1
| 1

reach
"The BREAK trials demonstrated tumor regression and improved progression free survival in patients treated with dabrafenib 60."
Dabrafenib affects BRAFV600E orBRAFV600K mutation
| 1
Dabrafenib activates BRAFV600E orBRAFV600K mutation. 1 / 1
| 1

reach
"In the BREAK-MB study [XREF_BIBR], 172 patients with asymptomatic brain metastases and BRAFV600E orBRAFV600K mutation were treated with dabrafenib."
Dabrafenib affects BRAFV600E mutation
| 1
Dabrafenib activates BRAFV600E mutation. 1 / 1
| 1

reach
"While waiting for the planning of proton radiotherapy and based on the recent success reported in the literature on BRAF inhibitors in the presence of BRAFV600E mutation in craniopharyngioma [XREF_BIBR], the patient was treated with dabrafenib (Tafinlar) 150mg twice daily."
Dabrafenib affects BRAF-wild-type
| 1
Dabrafenib activates BRAF-wild-type. 1 / 1
| 1

reach
"In this study, BRAF V600E -mutant (BCPAP and K1) and BRAF-wild-type (TPC-1) PTC cells were treated with MAPKi (dabrafenib or selumetinib) or EZH2 inhibitor (tazemetostat), or in combination, and the expression of iodine metabolizing genes, radioiodine uptake, and toxicity were tested."
Dabrafenib affects BRAF-i+MEK-i
| 1
Dabrafenib activates BRAF-i+MEK-i. 1 / 1
| 1

reach
"We analyzed two melanoma cohorts treated with MAPK inhibitors : (i) One cohort with BRAF-i or BRAF-i+ MEK-i treatment (n = 15, 8 patients treated with dabrafenib, 3 patients treated with vemurafenib, and 4 patients treated with dabtrafenib+ trametinib) 36 and (ii) another cohort with BRAF-i treatment (n = 23, dabtrafenib or vemurafenib) 37."
Dabrafenib affects BRAF-MEK
| 1
Dabrafenib inhibits BRAF-MEK. 1 / 1
| 1

reach
"Dual BRAF-MEK inhibition by dabrafenib and trametinib (both GlaxoSmithKline, Philadelphia, PA, USA) in BRAF V600E/K -mutant melanoma has been observed to be more durable as compared with monotherapy using a BRAF inhibitor."
Dabrafenib affects BRAF melanoma cell lines
| 1
Dabrafenib inhibits BRAF melanoma cell lines. 1 / 1
| 1

eidos
"Vemurafenib , encorafenib and dabrafenib induce cell cycle arrest and apoptosis in BRAF melanoma cell lines ; however , a residual population of tumor cells survive ."
Dabrafenib affects BRAF inhibitor
| 1
Dabrafenib inhibits BRAF inhibitor. 1 / 1
| 1

reach
"We illustrate an unexpected diagnosis of extensive bilateral pedal Kaposi sarcoma masquerading as BRAF inhibitor related toxicity in a patient treated with dabrafenib for metastatic melanoma."
Dabrafenib affects BIRC2
| 1
| 1

reach
"Neither Sorafenib nor GSK ' 872 or Dabrafenib prevented the BV6 stimulated downregulation of cIAP1."
Dabrafenib affects B-Raf inhibitor
| 1
Dabrafenib inhibits B-Raf inhibitor. 1 / 1
| 1

reach
"Taken together, we verified that dabrafenib triggers both autophagy and ER stress in both B-Raf inhibitor sensitive and B-Raf inhibitor resistant melanoma cells."
Dabrafenib affects B-Raf 34
| 1
Dabrafenib inhibits B-Raf 34. 1 / 1
| 1

reach
"The small-molecule kinase inhibitors included lapatinib, which inhibits epidermal growth factor receptor 33, dabrafenib, which inhibits B-Raf 34, trametinib, which inhibits MEK1 and MEK2 35, dinaciclib, which inhibits CDK1 and CDK5 36, and rigosertib, which inhibits polo like kinase 1 37."
Dabrafenib affects B-RAF kinase]
| 1
Dabrafenib inhibits B-RAF kinase]. 1 / 1
| 1

reach
"[Dabrafenib : the new inhibitor of hyperactive B-RAF kinase]."
Dabrafenib affects ATP
| 1

reach
"By competitively binding of ATP to the enzyme protein dabrafenib inhibited RIP3 with high selectivity relative to other RIP family members."
Dabrafenib affects ARAF
| 1

reach
"Dabrafenib bound to BRAF and ARAF with IC 50 of 6 and 26 nM, respectively, while its binding affinity to CRAF displayed an IC 50 of 150 nM, ~ 25-fold less than BRAF."
Dabrafenib affects A375VR4
| 1
Dabrafenib activates A375VR4. 1 / 1
| 1

reach
"We observed that the combination of vemurafenib or dabrafenib with TH1579 significantly reduced cell proliferation and induced cell death (p < 0.01) in A375, A375VR4, and ESTDAB049 cell lines compared with either treatment alone."
Dabrafenib affects 3D
| 1
| 1

reach
"Co-treatment of both A100 and dabrafenib significantly suppressed in vitro cell proliferation and three- dimensional (3D) matrigel growth."

reach
"In preclinical studies, there is strong evidence for the interaction of vemurafenib, dabrafenib, trametinib, palbociclib, cobimetinib and omipalisib with P-gp and BCRP."
Brivanib affects liver injury
| 1
Brivanib inhibits liver injury. 1 / 1
| 1

medscan
"We explored the therapeutic potential of brivanib to prevent or treat liver fibrosis associated with chronic liver injury in adult male C57BL/6J mice subjected to bile duct ligation and allowed to recover for 7 days from the procedure, followed by oral administration of placebo or brivanib for another 7 days."
Brivanib affects hypoxia-induced migration tube microvascular endothelial cells
| 1
Brivanib inhibits hypoxia-induced migration tube microvascular endothelial cells. 1 / 1
| 1

eidos
"In vitro , brivanib inhibits the hypoxia-induced proliferation , migration , and tube formation of microvascular endothelial cells ."
Brivanib affects growth factors
| 1
Brivanib inhibits growth factors. 1 / 1
| 1

medscan
"Brivanib decreases the transcription of growth factors and their receptors in CCl4-induced liver fibrosis, as seen in the results of mRNA expression determined by real time PCR ( ). (A) Histological analysis of livers from placebo and brivanib (25, 50, and 100 mg/kg) groups at 4 weeks after the initiation of carbon tetrachloride (CCl4)."
Brivanib affects VEGFA
| 1
Brivanib inhibits VEGFA. 1 / 1
| 1

medscan
"While brivanib inhibits VEGF and fibroblast growth factor, both of which are related to liver fibrosis, the effect of brivanib on liver fibrosis has not been previously studied."
Brivanib affects VEGF
| 1
Brivanib inhibits VEGF. 1 / 1
| 1

medscan
"Our findings that brivanib inhibits not only VEGF- and fibroblast growth factor-mediated proliferation of hepatic stellate cells, but also inhibits platelet-derived growth factor-induced proliferation, together with our other findings that brivanib abrogates phosphorylation of the platelet-derived growth factorβ receptor, suggest the need to further characterize the modulation of platelet-derived growth factor signaling by brivanib."
Brivanib affects PDGFRB
| 1
Brivanib inhibits PDGFRB. 1 / 1
| 1

medscan
"Our findings that brivanib inhibits not only VEGF- and fibroblast growth factor-mediated proliferation of hepatic stellate cells, but also inhibits platelet-derived growth factor-induced proliferation, together with our other findings that brivanib abrogates phosphorylation of the platelet-derived growth factorβ receptor, suggest the need to further characterize the modulation of platelet-derived growth factor signaling by brivanib."
Brivanib affects PDGF
| 1
Brivanib inhibits PDGF. 1 / 1
| 1

medscan
"Our findings that brivanib inhibits not only VEGF- and fibroblast growth factor-mediated proliferation of hepatic stellate cells, but also inhibits platelet-derived growth factor-induced proliferation, together with our other findings that brivanib abrogates phosphorylation of the platelet-derived growth factorβ receptor, suggest the need to further characterize the modulation of platelet-derived growth factor signaling by brivanib."
Brivanib affects Neoplasms
| 1
Brivanib inhibits Neoplasms. 1 / 1
| 1

medscan
"Here, we show that brivanib demonstrates antitumor activity in a broad range of xenograft models over multiple dose levels and that brivanib alaninate shows dose-dependent efficacy equivalent to brivanib in L2987 human tumor xenografts."
Brivanib affects KDR
| 1
Brivanib inhibits KDR. 1 / 1
| 1

medscan
"We hypothesized that inhibition of VEGFR and fibroblast growth factor receptor by brivanib would inhibit liver fibrosis."
Brivanib affects FGFR
| 1
Brivanib inhibits FGFR. 1 / 1
| 1

medscan
"We hypothesized that inhibition of VEGFR and fibroblast growth factor receptor by brivanib would inhibit liver fibrosis."
Y-39983 affects CWC22
| 1
Y-39983 activates CWC22. 1 / 1
| 1

reach
"We found that Y-39983 (ROCK I inhibitor), phenylbenzodioxane (ROCK II inhibitor), and thiazovivin (a novel ROCK inhibitor) can also modulate single-cell plating and promote NCM growth."
Y-27632 affects µ
| 1
Y-27632 inhibits µ. 1 / 1
| 1

reach
"Disrupted organoids were then resuspended in 100 µl concentrated lentivirus solution containing 8 µM polybrene (Sigma), 10 µM Y-27632 (Sigma) and 10 µM SB431542 (Sigma)."
| DOI
Y-27632 affects viral RNA replication
| 1
Y-27632 inhibits viral RNA replication. 1 / 1
| 1

eidos
"NSC23766 and Y27632 , the inhibitors of Rac1 and ROCK , respectively , similarly failed to reduce either viral RNA replication or viral RNA release into the culture supernatant , consistent with their inability to prevent viral gene expression ."
Y-27632 affects viral RNA release
| 1
Y-27632 inhibits viral RNA release. 1 / 1
| 1

eidos
"NSC23766 and Y27632 , the inhibitors of Rac1 and ROCK , respectively , similarly failed to reduce either viral RNA replication or viral RNA release into the culture supernatant , consistent with their inability to prevent viral gene expression ."
Y-27632 affects tongue squamous cell carcinoma
| 1
Y-27632 inhibits tongue squamous cell carcinoma. 1 / 1
| 1

medscan
"The study concludes that Y-27632 can inhibit the growth, invasion, and migration of Tca8113 and CAL-27 cells, suggesting that Y-27632 may be therapeutically useful in tongue squamous cell carcinoma."
Y-27632 affects survival
| 1
Y-27632 activates survival. 1 / 1
| 1

medscan
"Administration of Y-27632 prevents apoptosis and enhances survival of human embryonic stem cells at low culture density [Watanabe et al., ], possibly through the regulation of myosin light chain phosphorylation and cell-cell interactions [Harb et al., ]."
Y-27632 affects survival growth PSCs
| 1
Y-27632 activates survival growth PSCs. 1 / 1
| 1

eidos
"In 2007 , Y-27632 ( [ 1R ,4 r ] -4 - [ ( R ) -1 - aminoethyl ] - N - [ pyridin-4-yl ] cyclohexane carboxamide ) , the first small molecule to inhibit the Rho-associated kinase ( ROCK ) pathway , was reported to increase the survival and growth of PSCs ; since then , it has been used extensively in stem cell research [ 12 ] ."
Y-27632 affects stress fibers cultured cells
| 1
Y-27632 inhibits stress fibers cultured cells. 1 / 1
| 1

eidos
"Y-27632 also suppresses formation of stress fibers in cultured cells and decreases hypertension in several hypertensive rat models [ 109,110,111 ] ."
Y-27632 affects stress fiber
| 1
Y-27632 inhibits stress fiber. 1 / 1
| 1

medscan
"Y-27632, a selective ROCK inhibitor, suppressed RhoA-induced formation of actin stress fibers and formation of focal contact in trophoblast cells."
Y-27632 affects spindle formation
| 1
Y-27632 activates spindle formation. 1 / 1
| 1

medscan
"Multinucleated cells were not increased upon ARHGEF10 knockdown in contrast to treatment with Y-27632, a specific pharmacological inhibitor for the RhoA effector kinase ROCK, which induced not only multipolar spindle formation, but also multinucleation."

reach
"Furthermore, Y-27632, an inhibitor of ROCK2, attenuated the Ang II-induced contraction of HASMCs by blocking the RhoA/ROCK2 signaling pathway which is involved in this contraction, and thus may be a major regulator involved in the basal maintenance of contractility in HASMCs."
Y-27632 affects p-Tyr216 GSK-3beta
| 1
Y-27632 inhibits p-Tyr216 GSK-3beta. 1 / 1
| 1

eidos
"Indeed , p-Tyr216 GSK-3beta was increased by Abeta ( 1 muM ) , but was inhibited by Tat-C3 and Y27632 ( Fig. 2C ) ."
Y-27632 affects p-Ser422 Tau
| 1
Y-27632 inhibits p-Ser422 Tau. 1 / 1
| 1

eidos
"Furthermore , Tat-C3 ( Rho inhibitor ) , Y27632 ( ROCK inhibitor ) and LiCl ( GSK inhibitor ) prevented an increase in p-Ser422 Tau levels , but increased ACL levels irrespective of Abeta , showing an inverses relationship between p-Ser422 Tau and ACL expression ( Fig. 1 , Fig. 2 , Fig. 3E ) ."
Y-27632 affects only fibrosis
| 1
Y-27632 inhibits only fibrosis. 1 / 1
| 1

eidos
"Both candesartan cilexetil and Y27632 remarkably reduced not only fibrosis , but also severe steatosis and the liver weight of the treated rats was significantly reduced in both treated groups ."
| PMC
Y-27632 affects neutrophil adhesion
| 1
Y-27632 activates neutrophil adhesion. 1 / 1
| 1

medscan
"Similarly, Y-27632 treatment increased stimulated beta(2) integrin-dependent neutrophil adhesion at 30 min but not at 5 min."
Y-27632 affects motor function
| 1
Y-27632 activates motor function. 1 / 1
| 1

medscan
"Y-27632 also attenuates huntingtin toxicity in Drosophila and improves motor function in mice , ."
Y-27632 affects mitochondrial respiration
| 1
Y-27632 activates mitochondrial respiration. 1 / 1
| 1

medscan
"To our knowledge, the present study provides the first demonstration that Y-27632 treatment restores mitochondrial respiration, which is altered in senescent Hutchinson-Gilford progeria syndrome fibroblasts, through increasing the efficiency of Oxidative phosphorylation."
Y-27632 affects migration corneal endothelial cells
| 1
Y-27632 activates migration corneal endothelial cells. 1 / 1
| 1

eidos
"However , several studies reported that Y27632 promoted the migration and proliferation of corneal endothelial cells [ 22 ] , which might remind us that Y27632 has different mechanisms for different cell types , and the specific mechanisms of Rho kinase inhibitors on LECs need further elaboration ."
Y-27632 affects intraocular pressure
| 1
Y-27632 inhibits intraocular pressure. 1 / 1
| 1

medscan
"Rho-associated protein kinase Inhibitor, Y-27632 was tested for lowering intraocular pressure on Vav2-/-Vav3-/- mice (n = 20)."
Y-27632 affects internalization
| 1
Y-27632 inhibits internalization. 1 / 1
| 1

medscan
"This internalization was also inhibited by Y-27632, which suggested that ROCK activation is critical for internalization and desensitization of GPR39."
Y-27632 affects inflammatory response
| 1
Y-27632 inhibits inflammatory response. 1 / 1
| 1

medscan
"Oral administration of Y-27632 in rats significantly reduced the colonic inflammation."
Y-27632 affects huntingtin toxicity
| 1
Y-27632 inhibits huntingtin toxicity. 1 / 1
| 1

medscan
"Y-27632 also attenuates huntingtin toxicity in Drosophila and improves motor function in mice , ."
Y-27632 affects functional recovery
| 1
Y-27632 activates functional recovery. 1 / 1
| 1

medscan
"Taken together, the findings from our study suggest that rho-associated protein kinase inactivation with Y-27632 facilitates the functional recovery of mitochondria by inducing metabolic reprogramming."
Y-27632 affects focal adhesion
| 1
Y-27632 inhibits focal adhesion. 1 / 1
| 1

medscan
"Y-27632, a selective ROCK inhibitor, suppressed RhoA-induced formation of actin stress fibers and formation of focal contact in trophoblast cells."
Y-27632 affects filamentous connections cells
| 1
Y-27632 activates filamentous connections cells. 1 / 1
| 1

eidos
"As in control cells , Y-27632 further increased the number of filamentous connections in shP120 cells ( Fig. 4a , b ; compare Fig. 2g , h ) ; however , in p120low cells , ROCK inhibition failed to restore both network organization and invasion into astrocyte scaffolds ( Fig. 4b ) ."
Y-27632 affects enhanced neurite outgrowth
| 1
Y-27632 activates enhanced neurite outgrowth. 1 / 1
| 1

eidos
"Notably , inhibition of RhoA and ROCK by Tat-C3 and Y27632 , respectively , enhanced neurite outgrowth ( Fig. 3A ) [ [ 17 ] , [ 18 ] , [ 19 ] ] ."
Y-27632 affects effector kinase protein kinase
| 1
Y-27632 inhibits effector kinase protein kinase. 1 / 1
| 1

eidos
"As previously demonstrated in other cell types , nocodazole treatment triggered a global increase of RhoA activity and myosin light chain ( MLC ) phosphorylation ( Liu et al ., 1998 ; Takesono et al ., 2010 ; Fig. S2 , d and e ) , and pharmacological inhibition of the effector kinase Rho-associated protein kinase ( ROCK ) by Y27632 reverted this effect ."
Y-27632 affects cytoskeleton rearrangement hyper-permeability HUVECs induced TNF-alpha
| 1
Y-27632 activates cytoskeleton rearrangement hyper-permeability HUVECs induced TNF-alpha. 1 / 1
| 1

eidos
"ROCK inhibitor Y-27632 obviously inhibited the cytoskeleton rearrangement and hyper-permeability of HUVECs induced by TNF-alpha ."
Y-27632 affects corneal wound healing
| 1
Y-27632 activates corneal wound healing. 1 / 1
| 1

eidos
"The Rho-associated , coiled-coil-containing protein kinase ( ROCK ) inhibitor ( Y27632 ) has been shown to promote corneal wound healing and cell proliferation [ 32 , 33 ] ; we found that supplementation with Y27632 was critical for explant outgrowth in this medium ."
Y-27632 affects contraction HASMCs
| 1
Y-27632 inhibits contraction HASMCs. 1 / 1
| 1

eidos
"Furthermore , Y-27632 , an inhibitor of ROCK2 , attenuated the Ang II-induced contraction of HASMCs by blocking the RhoA / ROCK2 signaling pathway which is involved in this contraction , and thus may be a major regulator involved in the basal maintenance of contractility in HASMCs ."
Y-27632 affects contractility in human airway smooth muscle cells
| 1
Y-27632 inhibits contractility in human airway smooth muscle cells. 1 / 1
| 1

medscan
"Furthermore, Y-27632, an inhibitor of ROCK2, attenuated the Angiotensin II-induced contraction of human airway smooth muscle cells by blocking the RhoA/ROCK2 signaling pathway which is involved in this contraction, and thus may be a major regulator involved in the basal maintenance of contractility in human airway smooth muscle cells."
Y-27632 affects contractile force tracheal smooth muscle guinea pig
| 1
Y-27632 inhibits contractile force tracheal smooth muscle guinea pig. 1 / 1
| 1

eidos
"Further studies suggest one of the important mechanisms that Mfge8 could suppress contraction of airway smooth muscles through inhibiting RhoA.66 Sphingosine-1-phosphate ( S1P : a bioactive lysophospholipid ) has been shown to increase the contraction tension in isolated BSM tissues when they are pre-depolarised by K + , and was attenuated by Y-27632.67Similarly , S1P markedly enhanced contractile force of tracheal smooth muscle in guinea pig , which was also inhibited by Y-27632 ."
Y-27632 affects chemotaxis of the cells
| 1
Y-27632 inhibits chemotaxis of the cells. 1 / 1
| 1

medscan
"Both a Rho inhibitor C3 exoenzyme and a Rho kinase (ROCK) inhibitor Y-27632 inhibited chemotaxis of rat basophilic leukemia-2H3 cells expressing human CCR1 cells toward CCL3, indicating that activation of the Rho/ROCK signaling pathway is required for the CCL3-mediated chemotaxis of the cells."
Y-27632 affects cellular migration
| 1
Y-27632 activates cellular migration. 1 / 1
| 1

medscan
"Consistent with this possibility, treatment with the Rho-associated kinase-selective Y-27632 pharmacologic inhibitor reversed the accumulation of abnormal actin stress fibers and focal adhesion enlargement observed in TEM4-depleted cells ( A, B) and, more importantly, restored persistence of cellular migration of human umbilical vein primary endothelial cells depleted of TEM4 ( C-E and )."
Y-27632 affects cell-cell junction
| 1
Y-27632 inhibits cell-cell junction. 1 / 1
| 1

medscan
"E-cadherin- and beta-catenin-mediated cell-cell junction and actin cytoskeleton organization were disrupted by Y-27632."

eidos
"The Rho-associated , coiled-coil-containing protein kinase ( ROCK ) inhibitor ( Y27632 ) has been shown to promote corneal wound healing and cell proliferation [ 32 , 33 ] ; we found that supplementation with Y27632 was critical for explant outgrowth in this medium ."
Y-27632 affects cell motility
| 1
Y-27632 inhibits cell motility. 1 / 1
| 1

medscan
"The ROCK inhibitor Y-27632 decreased cell motility (P < 0.01, Student's t-test; n = 4) (Fig. d)."
Y-27632 affects cell migration and adhesion
| 1
Y-27632 activates cell migration and adhesion. 1 / 1
| 1

medscan
"Y-27632 promoted basal and HB-EGF-enhanced scratch wound healing and enhanced cell migration and adhesion to matrices, while retarded HB-EGF induced cell proliferation."
Y-27632 affects cell death
| 1
Y-27632 activates cell death. 1 / 1
| 1

medscan
"To confirm that Y-27632 treatment induces cell death, we treated RCC4 and RCC4Von Hippel Lindau cells with 20µM Y-27632 for 24 hours and then stained the cells with propidium iodide ."
Y-27632 affects cAMP-dependent protein kinase concentrations.27
| 1
Y-27632 inhibits cAMP-dependent protein kinase concentrations.27. 1 / 1
| 1

eidos
"Both have similar activity as Y-27632 , which can inhibit cAMP-dependent protein kinase at relatively low concentrations.27 ,28 However , none of these were applied for the treatment of asthma ."
Y-27632 affects bicellular tight junction
| 1
| 1

medscan
"Y-27632 impaired the formation and maintenance of tight junction barriers indicated by decreased trans-epithelial resistance and disrupted occludin staining."
Y-27632 affects axonal growth
| 1
Y-27632 activates axonal growth. 1 / 1
| 1

eidos
"These results indicate that Y27632 and diltiazem additively enhance axonal growth in the presence of CSPGs ."
Y-27632 affects axon
| 1
Y-27632 activates axon. 1 / 1
| 1

eidos
"Y27632 increases DRG axon length up to 2.0-fold on CSPG ( Supplementary Fig. 2A ) , with an EC50 of 5.9 + / - 1.2 muM ."
Y-27632 affects arctiin-induced VEGF
| 1
Y-27632 inhibits arctiin-induced VEGF. 1 / 1
| 1

eidos
"In addition , Y-27632 attenuated arctiin-induced VEGF down-regulation and G0 / G1 phase cell cycle arrest ."
Y-27632 affects anoikis
| 1
Y-27632 inhibits anoikis. 1 / 1
| 1

medscan
"Given that treatment with the ROCK inhibitor Y-27632 prevents anoikis [ ], tumor cells harboring the ROCK1 nonsense mutation might be resistant to anoikis through the impairment of the Rho-ROCK pathway, similar to tumor cells harboring the RHOA L57V mutation. 46999999="L57V"}"
Y-27632 affects actomyosin
| 1
Y-27632 inhibits actomyosin. 1 / 1
| 1

medscan
"The ROCK inhibitor Y-27632 decreases regulatory light chain phosphorylation, resulting in the loss of actomyosin filament bundles and a concomitant up-regulation in Rac1 activity ( ; ; )."
Y-27632 affects actin-stress fiber formation
| 1
Y-27632 inhibits actin-stress fiber formation. 1 / 1
| 1

medscan
"Moreover, inhibition of either Rho with exoenzyme C3 or ROCK with Y-27632 attenuated VEGF-induced increases in permeability, myosin light chain phosphorylation, and actin-stress fiber formation in coronary venular endothelial cell monolayers."

eidos
"We also noted that feeder cells and altered molecular pathways activate telomerase ( Fu et al. 2003 ; Liu et al. 2008 ; Liu et al. 2009 ; Klingelhutz and Roman 2012 ; Liu et al. 2012 ) , and a Rho-Kinase inhibitor , Y-27632 , disrupts the actin cytoskeleton and inactivate Rho ( Chapman et al. 2010 ; Liu et al. 2012 ) ."
| PMC
Y-27632 affects actin cytoskeleton organization
| 1
Y-27632 inhibits actin cytoskeleton organization. 1 / 1
| 1

medscan
"E-cadherin- and beta-catenin-mediated cell-cell junction and actin cytoskeleton organization were disrupted by Y-27632."
Y-27632 affects a-SMA
| 1
Y-27632 activates a-SMA. 1 / 1
| 1

eidos
"Simvastatin , a commonly used HMG-COA reductase inhibitor , causes attenuation of BSMC via geranylgeranylation of RhoA.55The Rho-kinase inhibitor Y-27632 decreased the expression levels of F-actin and alpha-tubulin , suggesting a link for Rho-kinase and airway smooth muscle cytoskeleton in airway remodelling in asthma.73Furthermore , sphingosylphosphorylcholine ( SPC ) , a sphingolipid metabolite , could stimulate a-SMA expression in human foetal lung fibroblast and fibroblast-mediated collagen gel contraction.74Of interest , the increased expression of a-SMA was blocked by Y-27632 , indicating that RhoA signalling may be involved in SPC-induced airway remodelling in asthma ."
Y-27632 affects Y-27632.67Similarly
| 1
Y-27632 inhibits Y-27632.67Similarly. 1 / 1
| 1

eidos
"Further studies suggest one of the important mechanisms that Mfge8 could suppress contraction of airway smooth muscles through inhibiting RhoA.66 Sphingosine-1-phosphate ( S1P : a bioactive lysophospholipid ) has been shown to increase the contraction tension in isolated BSM tissues when they are pre-depolarised by K + , and was attenuated by Y-27632.67Similarly , S1P markedly enhanced contractile force of tracheal smooth muscle in guinea pig , which was also inhibited by Y-27632 ."
Y-27632 affects Wounds and Injuries
| 1
Y-27632 activates Wounds and Injuries. 1 / 1
| 1

medscan
"Y-27632 promoted basal and HB-EGF-enhanced scratch wound healing and enhanced cell migration and adhesion to matrices, while retarded HB-EGF induced cell proliferation."
Y-27632 affects VCL
| 1
Y-27632 inhibits VCL. 1 / 1
| 1

medscan
"Video 6 shows that Y-27632 inhibits thrombin-induced junction remodeling in human umbilical vein endothelial cells expressing Vinculin-GFP and p120-catenin-mCherry."
Y-27632 affects TNF
| 1
Y-27632 decreases the amount of TNF. 1 / 1
| 1

medscan
"Y-27632 inhibited production of tumor necrosis factor-alpha and interleukin-1 beta by lamina propria and peripheral blood mononuclear cells."
Y-27632 affects TJP1
| 1
Y-27632 increases the amount of TJP1. 1 / 1
| 1

medscan
"However, expression of ZO-1 was upregulated by Y-27632 but not significantly affected by Lysophosphatidic acid after odontoblast differentiation."
Y-27632 affects TGEV binding
| 1
Y-27632 activates TGEV binding. 1 / 1
| 1

eidos
"ROCK inhibitor Y27632 did not inhibit TGEV binding as well as TGEV entry ( Figure 3A ) ."
Y-27632 affects RhoA downstream effector
| 1
Y-27632 inhibits RhoA downstream effector. 1 / 1
| 1

eidos
"Y27632 inhibits the RhoA downstream effector , Rho-associated coiled-coil-forming kinase ( ROCK ) [ 113 ] ."
| PMC
Y-27632 affects Rho-associating protein kinase
| 1
Y-27632 inhibits Rho-associating protein kinase. 1 / 1
| 1

eidos
"Y27632 inhibits Rho-associating protein kinase ( ROCK ) ."
Y-27632 affects Rho-associated kinase
| 1
Y-27632 inhibits Rho-associated kinase. 1 / 1
| 1

medscan
"Inhibition of Rho-associated kinase by Y-27632 reduced the FPR-mediated inotropic effect and MLC-2 phosphorylation by approximately 40-45% and MYPT-2 phosphorylation by approximately 70%."
Y-27632 affects Rho-associated kinase pathway
| 1
Y-27632 inhibits Rho-associated kinase pathway. 1 / 1
| 1

medscan
"Inhibition of the Rho-associated kinase pathway with the inhibitor Y-27632 restored the ability of γ-actin-knockdown cells to migrate."
Y-27632 affects Rho-associated coiled-coil containing protein kinase (ROCK
| 1
Y-27632 inhibits Rho-associated coiled-coil containing protein kinase (ROCK. 1 / 1
| 1

medscan
"The objective of this study is to determine the effects of Rho-associated coiled-coil containing protein kinase (ROCK) inhibitor Y-27632 on the growth, invasion, and migration of Tca8113 and CAL-27 cells in tongue squamous cell carcinoma ."
Y-27632 affects Rho associated kinase
| 1
Y-27632 inhibits Rho associated kinase. 1 / 1
| 1

medscan
"Inhibition of Rho associated kinase by Y-27632 inhibited the activity of Ras homologue A and promoted the apoptosis."
| 1
| 1

eidos
"This relaxation was strongly inhibited by the Rho-kinase inhibitor Y-27632 ( 10 muM ) , by the reducing agent DTT or by the inhibitor of soluble guanylate cyclase ( sGC ) ODQ ( 10 muM ) alone or in combination with the inhibitors of the endogenous synthesis of H 2 S beta-cyano-L-alanine ( 5 mM ) and amino-oxyacetate ( 5 mM ) ."
Y-27632 affects RPS6KA5
1 |
1 |

tas
No evidence text available
Y-27632 affects ROCK signaling pathway
| 1
Y-27632 inhibits ROCK signaling pathway. 1 / 1
| 1

medscan
"Both a Rho inhibitor C3 exoenzyme and a Rho kinase (ROCK) inhibitor Y-27632 inhibited chemotaxis of rat basophilic leukemia-2H3 cells expressing human CCR1 cells toward CCL3, indicating that activation of the Rho/ROCK signaling pathway is required for the CCL3-mediated chemotaxis of the cells."
Y-27632 affects RDX
| 1
Y-27632 decreases the amount of RDX. 1 / 1
| 1

medscan
"Y-27632 reduced the expression levels of phosphorylated ezrin, radixin, and moesin in angiotensin II-treated Wistar-Kyoto rats and spontaneously hypertensive rats."
Y-27632 affects RAC1
| 1
Y-27632 inhibits RAC1. 1 / 1
| 1

medscan
"The ROCK inhibitor Y-27632 decreases regulatory light chain phosphorylation, resulting in the loss of actomyosin filament bundles and a concomitant up-regulation in Rac1 activity ( ; ; )."
| 1

eidos
"Next , DLD-1 vector and hGPR56 cells were treated with Rho inhibitor I , a cell permeable C3 transferase which inhibits Rho , or Y27632 which inhibits Rho-associated protein kinase ( ROCK ) , a kinase activated by RhoA ."
Y-27632 affects Progeria
| 1
Y-27632 inhibits Progeria. 1 / 1
| 1

medscan
"rho-associated protein kinase regulates mitochondrial function by inducing metabolic reprogramming. (A) Measurement of extracellular acidification rate (black line: young Hutchinson-Gilford progeria syndrome fibroblasts, blue line: Y-27632-treated senescent Hutchinson-Gilford progeria syndrome fibroblasts, green line: Y-27632/DFP-treated senescent Hutchinson-Gilford progeria syndrome fibroblasts, and red line: DMSO-treated senescent Hutchinson-Gilford progeria syndrome fibroblasts; **P < 0.01, one-way ANOVA)."
Y-27632 affects PTHLH
| 1
Y-27632 inhibits PTHLH. 1 / 1
| 1

medscan
"Similarly, treatment of MDA-MB-231 cells with the Rho-associated kinase inhibitor Y-27632 inhibits (C) Gli2 and (D) PTHrP expression."
Y-27632 affects PRKX
1 |
Y-27632 inhibits PRKX. 1 / 1
1 |

tas
No evidence text available
Y-27632 affects PRKCQ
1 |
1 |

tas
No evidence text available
Y-27632 affects PRKCE
1 |
1 |

tas
No evidence text available
Y-27632 affects PRKCD
1 |
1 |

tas
No evidence text available
Y-27632 affects PRKACA
1 |
1 |

drugbank
No evidence text available
Y-27632 affects PKIA
1 |
Y-27632 inhibits PKIA. 1 / 1
1 |

drugbank
No evidence text available
Y-27632 affects PI3K
| 1
Y-27632 inhibits PI3K. 1 / 1
| 1

medscan
"Y-27632 did not inhibit other well known survival pathways, such as NF-kappa B, ERK, and phosphatidylinositol 3-kinase/Akt."
Y-27632 affects PFN
| 1
Y-27632 inhibits PFN. 1 / 1
| 1

medscan
"Y-27632 blocks phosphorylation of profilin, an actin-binding protein that directly binds huntingtin, but not androgen receptor , ."
Y-27632 affects Neoplasm Metastasis
| 1
Y-27632 inhibits Neoplasm Metastasis. 1 / 1
| 1

medscan
"Inhibiting Rho-associated kinase 1/2 activity with Y-27632, a Rho-associated kinase 1/2 inhibitor abrogated the pro-migration and pro-metastasis effects of GCs in vitro and in vivo, indicating that Rho-associated kinase 1/2 mediated the pro-metastasis effects of GCs."
Y-27632 affects NFkappaB
| 1
Y-27632 inhibits NFkappaB. 1 / 1
| 1

medscan
"Y-27632 did not inhibit other well known survival pathways, such as NF-kappa B, ERK, and phosphatidylinositol 3-kinase/Akt."
Y-27632 affects MOVEMENT
| 1
Y-27632 inhibits MOVEMENT. 1 / 1
| 1

trips
"Moreover, the alphabetaMeATP-elicited neutrophil movements were prevented by the two Rho kinase inhibitors, Y27632 and H1152."
Y-27632 affects MAPK3
| 1
Y-27632 inhibits MAPK3. 1 / 1
| 1

medscan
"Furthermore, pretreatment with Y-27632, an inhibitor of ROCK, significantly reduced lipopolysaccharide-induced p38, ERK1/2 and p65 phosphorylation, indicating that ROCK acts as an upstream effector of p38 and ERK1/2 to promote lipopolysaccharide-induced NF-κB transactivation and ICAM-1 expression."
Y-27632 affects MAPK1
| 1
Y-27632 inhibits MAPK1. 1 / 1
| 1

medscan
"Y-27632 did not inhibit other well known survival pathways, such as NF-kappa B, ERK, and phosphatidylinositol 3-kinase/Akt."
Y-27632 affects Liver Neoplasms
| 1
Y-27632 inhibits Liver Neoplasms. 1 / 1
| 1

medscan
"The finding that invasiveness of hepatocellular carcinoma is facilitated by the Rho/Rho-kinase pathway is likely to be relevant to tumor progression and Y-27632 may be a new potential effective agent for the prevention of intrahepatic extension of human liver cancer."
Y-27632 affects Leukemia, Basophilic, Acute
| 1
| 1

medscan
"Both a Rho inhibitor C3 exoenzyme and a Rho kinase (ROCK) inhibitor Y-27632 inhibited chemotaxis of rat basophilic leukemia-2H3 cells expressing human CCR1 cells toward CCL3, indicating that activation of the Rho/ROCK signaling pathway is required for the CCL3-mediated chemotaxis of the cells."
Y-27632 affects LRRK2
1 |
1 |

tas
No evidence text available
Y-27632 affects LIMK2
| 1
Y-27632 inhibits LIMK2. 1 / 1
| 1

medscan
"Y-27632 or ROCK-1 short interfering RNA inhibits LIMK2/cofilin pathway."
Y-27632 affects LIM-kinase
| 1
Y-27632 increases the amount of LIM-kinase. 1 / 1
| 1

medscan
"Overexpression of LIM-kinase in HeLa cells induced the formation of actin stress fibers in a Y-27632-sensitive manner."
Y-27632 affects Integrins
| 1
Y-27632 activates Integrins. 1 / 1
| 1

medscan
"ROCK-2 inhibitor Y-27632 increases the expression of genes of stemness-related integrins (αV, α6 and β1), which in turn increase ECM-cell interaction ."
Y-27632 affects INS
| 1
Y-27632 increases the amount of INS. 1 / 1
| 1

medscan
"Furthermore, using the luciferase reporter gene assay, insulin promoter activity was also dramatically increased by Y-27632, which was associated with an increase in the insulin mRNA level."
Y-27632 affects IL1B
| 1
Y-27632 decreases the amount of IL1B. 1 / 1
| 1

medscan
"Y-27632 inhibited production of tumor necrosis factor-alpha and interleukin-1 beta by lamina propria and peripheral blood mononuclear cells."
Y-27632 affects IL12B
| 1
Y-27632 increases the amount of IL12B. 1 / 1
| 1

medscan
"Interestingly, a Rho-associated protein kinase inhibitor (Y-27632) abolished the inhibition of lipopolysaccharide-stimulated IL-12p40 production by SP-D, whereas silencing of ERK 2 significantly blunted this effect of Y-27632."
Y-27632 affects I-kappa B kinase
| 1
Y-27632 inhibits I-kappa B kinase. 1 / 1
| 1

medscan
"We showed that Rho kinase associates with and activates I-kappa B kinase alpha and that Y-27632 prevents I-kappa B kinase activation."
Y-27632 affects Huntington Disease
| 1
Y-27632 inhibits Huntington Disease. 1 / 1
| 1

medscan
"Y-27632, an inhibitor of the Rho-associated kinase ROCK, is a therapeutic lead for Huntington disease ."
Y-27632 affects G0 G1 phase cell cycle
| 1
Y-27632 inhibits G0 G1 phase cell cycle. 1 / 1
| 1

eidos
"In addition , Y-27632 attenuated arctiin-induced VEGF down-regulation and G0 / G1 phase cell cycle arrest ."
Y-27632 affects Fig. 3A
| 1
Y-27632 activates Fig. 3A. 1 / 1
| 1

eidos
"Notably , inhibition of RhoA and ROCK by Tat-C3 and Y27632 , respectively , enhanced neurite outgrowth ( Fig. 3A ) [ [ 17 ] , [ 18 ] , [ 19 ] ] ."
Y-27632 affects FAT4
| 1
Y-27632 decreases the amount of FAT4. 1 / 1
| 1

medscan
"Y-27632 treatment decreased FAT4 mRNA expression."
Y-27632 affects F2
| 1
Y-27632 inhibits F2. 1 / 1
| 1

medscan
"We further demonstrated that inhibition of Rho with C3 exoenzyme or dominant negative RhoA, and inhibition of Rho-Kinase (ROCK) with Y-27632 caused a significant decrease in thrombin and TFLLR-induced Thr495 phosphorylation."
Y-27632 affects EZR
| 1
Y-27632 decreases the amount of EZR. 1 / 1
| 1

medscan
"Y-27632 reduced the expression levels of phosphorylated ezrin, radixin, and moesin in angiotensin II-treated Wistar-Kyoto rats and spontaneously hypertensive rats."
Y-27632 affects ERK
| 1
Y-27632 phosphorylates ERK. 1 / 1
| 1

isi
"The ROCK inhibitor Y-27632 significantly suppressed Pi-induced CypA secretion, ERK1/2 phosphorylation, and calcium accumulation."
Y-27632 affects CTNND1
| 1
Y-27632 inhibits CTNND1. 1 / 1
| 1

medscan
"Video 6 shows that Y-27632 inhibits thrombin-induced junction remodeling in human umbilical vein endothelial cells expressing Vinculin-GFP and p120-catenin-mCherry."
Y-27632 affects CLK4
1 |
Y-27632 inhibits CLK4. 1 / 1
1 |

tas
No evidence text available
Y-27632 affects CCL2
| 1
Y-27632 inhibits CCL2. 1 / 1
| 1

medscan
"Y-27632, a specific Rho-kinase inhibitor, potently inhibited MCP-1 induction by thrombin."
Y-27632 affects Axon growth
| 1
Y-27632 inhibits Axon growth. 1 / 1
| 1

eidos
"Axon growth was significantly inhibited by CSPG exposure and increased by Y27632 in the presence of CSPG ( Fig. 1B ) ."
Y-27632 affects Alzheimer Disease
| 1
Y-27632 inhibits Alzheimer Disease. 1 / 1
| 1

medscan
"Administration of Y-27632, a selective Rock inhibitor, also preferentially lowered brain levels of Abeta42 in a transgenic mouse model of Alzheimer's disease."
Y-27632 affects Acetylcholine-evoked contraction
| 1
Y-27632 inhibits Acetylcholine-evoked contraction. 1 / 1
| 1

eidos
"Acetylcholine-evoked contraction was also partially reduced by nifedipine ( a selective inhibitor of L-type voltage-dependent Ca 2 + channels , LVDCCs ) , YM-58483 ( a selective inhibitor of store-operated Ca 2 + entry , SOCE ) , as well as Y-27632 ( an inhibitor of Rho-associated protein kinase , ROCK ) ."
Y-27632 affects ARHGEF17
| 1
Y-27632 activates ARHGEF17. 1 / 1
| 1

medscan
"Treatment with Y-27632 restores persistence of human umbilical vein primary endothelial cells depleted of TEM4."
Y-27632 affects APP
| 1
Y-27632 inhibits APP. 1 / 1
| 1

eidos
"In addition , low concentration of Abeta ( 1 muM ) - induced p-Tyr416 Src was inhibited by Tat-C3 and Y27632 , suggesting that RhoA and ROCK regulate p-Tyr416 Src ( active ) upon low concentrations of Abeta , but LiCl ( GSK-3beta inhibitor ) did not impair p-Tyr416 Src ."
Y-27632 affects AHCYL1
| 1
Y-27632 inhibits AHCYL1. 1 / 1
| 1

medscan
"Furthermore we found that IRBIT sequestration can be prevented by a rho kinase inhibitor, Y-27632."
PD 407824 affects CHEK1
1 |
1 |

ctd
No evidence text available
LY-2157299 affects liver remodeling
| 1
LY-2157299 activates liver remodeling. 1 / 1
| 1

eidos
"Moreover , galunisertib promoted liver remodeling by proliferating hepatocytes and vascular endothelial cells , while significantly increasing liver weight ."
LY-2157299 affects cytokine secretion CAR T cells T cells
| 1
LY-2157299 activates cytokine secretion CAR T cells T cells. 1 / 1
| 1

eidos
"Galunisertib significantly increased the cytokine secretion of CAR T cells and T cells that do not express CAR ( Nontransfected T cells ) ."
LY-2157299 affects chimeric antigen receptor-modified T cell function
| 1
LY-2157299 activates chimeric antigen receptor-modified T cell function. 1 / 1
| 1

eidos
"Galunisertib enhances chimeric antigen receptor-modified T cell function ."
LY-2157299 affects cell invasion
| 1
LY-2157299 activates cell invasion. 1 / 1
| 1

medscan
"Although transforming growth factor-β (TGF-β) and hepatocyte growth factor (HGF) individually stimulated the tumor cell invasion into collagen gel without fibroblasts, TGF-β signaling inhibitors (SB431542 and LY2157299) significantly enhanced the Panc-1 cell invasion in the 3D co-culture with fibroblasts."
LY-2157299 affects WNT16
| 1
| 1

medscan
"Inhibition of Wnt16 expression is Smad-dependent and can be prevented by selective inhibitors of Smad2/3 signaling SB431542 and LY2157299 ( ), while BMP inhibitors have no effect."
LY-2157299 affects TGFβRI
| 1
LY-2157299 inhibits TGFβRI. 1 / 1
| 1

medscan
"Conversely, we observed that inhibition of the TGFβ signaling pathway by LY2157299, a TGFβRI kinase inhibitor, enhanced sorafenib-induced apoptosis, in vitro."
LY-2157299 affects TGFBR2
1 |
1 |

signor
No evidence text available
LY-2157299 affects SMAD2
| 1
| 1

medscan
"In keeping with our results, in a hepatocellular carcinoma cell line, LY2157299 blocked cell migration by activating SMAD2, but independently from TGF-b receptors [ ]."
LY-2157299 affects Raw264.7 cells
| 1
LY-2157299 inhibits Raw264.7 cells. 1 / 1
| 1

eidos
"Schistosoma japonicum egg antigens promoted the expression of Hsp47 , TGF-beta1 , Timp-1 , alpha-SMA , Col1A1 and Col3A1 in NIH3T3 cells , and TGF-beta1 , CTGF , IL-13 , IL-17 and IL-6 in Raw264.7 cells , which was inhibited by XCH , LY2157299 and shRNA-Hsp47 ."
LY-2157299 affects RIPK2
1 |
1 |

tas
No evidence text available
LY-2157299 affects MAPK14
1 |
1 |

tas
No evidence text available
LY-2157299 affects KDR
1 |
1 |

tas
No evidence text available
LY-2157299 affects EsoAd1 ALK7
| 1
LY-2157299 activates EsoAd1 ALK7. 1 / 1
| 1

eidos
"We note that , the increased growth suppression observed with SB431542 versus LY2157299 in EsoAdl , but not in FLO-1 ( Figure 4 , A and B ) , may reflect EsoAd1 's significant expression of ALK7 ( Supplementary Figure S13 ) that is inhibited by SB431542 but not by LY2157299 ."
LY-2157299 affects COL2A1
1 |
LY-2157299 decreases the amount of COL2A1. 1 / 1
1 |

ctd
No evidence text available
LY-2157299 affects CD8
| 1
LY-2157299 activates CD8. 1 / 1
| 1

reach
"PLA detected the significantly increased close proximity between ubiquitin and Smad4 in dLN cells, especially in CD8 + T cells of the melanoma bearing mice treated with EW-7197 or LY-2157299 (XREF_FIG A, Supporting Information XREF_SUPPLEMENTARY)."
LY-2157299 affects ACVR1B
1 |
1 |

tas
No evidence text available
LY-2157299 affects ACAN
1 |
LY-2157299 decreases the amount of ACAN. 1 / 1
1 |

ctd
No evidence text available
KW2449 affects vorinostat
| 1
| 1

reach
"Dose response studies revealed that KW2449 concentration as low as 0.2 microM potentiated the lethality of marginally toxic concentrations of vorinostat or SNDX-275 in K562 cells."
KW2449 affects aurora kinases
| 1
KW2449 inhibits aurora kinases. 1 / 1
| 1

reach
"Although the multi-kinase inhibitor KW2449, which also inhibits Bcr and Abl and aurora kinases, has primarily been developed as a FLT3 inhibitor in AML [XREF_BIBR], preclinical studies demonstrate that it effectively kills Bcr and Abl + leukemias, including Ph + ALL, bearing gatekeeper mutations [XREF_BIBR]."
KW2449 affects ZAP70
1 |
KW2449 inhibits ZAP70. 1 / 1
1 |

tas
No evidence text available
KW2449 affects YES1
1 |
KW2449 inhibits YES1. 1 / 1
1 |

tas
No evidence text available
KW2449 affects ULK3
1 |
KW2449 inhibits ULK3. 1 / 1
1 |

tas
No evidence text available
KW2449 affects ULK2
1 |
KW2449 inhibits ULK2. 1 / 1
1 |

tas
No evidence text available
KW2449 affects ULK1
1 |
KW2449 inhibits ULK1. 1 / 1
1 |

tas
No evidence text available
KW2449 affects TYK2
1 |
KW2449 inhibits TYK2. 1 / 1
1 |

tas
No evidence text available
KW2449 affects TXK
1 |
KW2449 inhibits TXK. 1 / 1
1 |

tas
No evidence text available
KW2449 affects TTK
1 |
KW2449 inhibits TTK. 1 / 1
1 |

tas
No evidence text available
KW2449 affects TNK1
1 |
KW2449 inhibits TNK1. 1 / 1
1 |

tas
No evidence text available
KW2449 affects TNIK
1 |
KW2449 inhibits TNIK. 1 / 1
1 |

tas
No evidence text available
KW2449 affects TIE1
1 |
KW2449 inhibits TIE1. 1 / 1
1 |

tas
No evidence text available
KW2449 affects TBK1
1 |
KW2449 inhibits TBK1. 1 / 1
1 |

tas
No evidence text available
KW2449 affects SYK
1 |
KW2449 inhibits SYK. 1 / 1
1 |

tas
No evidence text available
KW2449 affects STK4
1 |
KW2449 inhibits STK4. 1 / 1
1 |

tas
No evidence text available
KW2449 affects STK39
1 |
KW2449 inhibits STK39. 1 / 1
1 |

tas
No evidence text available
KW2449 affects STK38
1 |
KW2449 inhibits STK38. 1 / 1
1 |

tas
No evidence text available
KW2449 affects STK35
1 |
KW2449 inhibits STK35. 1 / 1
1 |

tas
No evidence text available
KW2449 affects STK33
1 |
KW2449 inhibits STK33. 1 / 1
1 |

tas
No evidence text available
KW2449 affects STK17B
1 |
1 |

tas
No evidence text available
KW2449 affects STK17A
1 |
1 |

tas
No evidence text available
KW2449 affects STK16
1 |
KW2449 inhibits STK16. 1 / 1
1 |

tas
No evidence text available
KW2449 affects STK11
1 |
KW2449 inhibits STK11. 1 / 1
1 |

tas
No evidence text available
KW2449 affects STK10
1 |
KW2449 inhibits STK10. 1 / 1
1 |

tas
No evidence text available
KW2449 affects SRPK3
1 |
KW2449 inhibits SRPK3. 1 / 1
1 |

tas
No evidence text available
KW2449 affects SRPK2
1 |
KW2449 inhibits SRPK2. 1 / 1
1 |

tas
No evidence text available
KW2449 affects SRPK1
1 |
KW2449 inhibits SRPK1. 1 / 1
1 |

tas
No evidence text available
KW2449 affects SNDX-275
| 1
KW2449 activates SNDX-275. 1 / 1
| 1

reach
"Dose response studies revealed that KW2449 concentration as low as 0.2 microM potentiated the lethality of marginally toxic concentrations of vorinostat or SNDX-275 in K562 cells."
KW2449 affects SLK
1 |
KW2449 inhibits SLK. 1 / 1
1 |

tas
No evidence text available
KW2449 affects SIK2
1 |
KW2449 inhibits SIK2. 1 / 1
1 |

tas
No evidence text available
KW2449 affects SIK1
1 |
KW2449 inhibits SIK1. 1 / 1
1 |

tas
No evidence text available
KW2449 affects SGK3
1 |
KW2449 inhibits SGK3. 1 / 1
1 |

tas
No evidence text available
KW2449 affects SBK3
1 |
KW2449 inhibits SBK3. 1 / 1
1 |

tas
No evidence text available
KW2449 affects SBK1
1 |
KW2449 inhibits SBK1. 1 / 1
1 |

tas
No evidence text available
KW2449 affects RPS6KB1
1 |
1 |

tas
No evidence text available
KW2449 affects RPS6KA3
1 |
1 |

tas
No evidence text available
KW2449 affects ROCK2
1 |
KW2449 inhibits ROCK2. 1 / 1
1 |

tas
No evidence text available
KW2449 affects ROCK1
1 |
KW2449 inhibits ROCK1. 1 / 1
1 |

tas
No evidence text available
KW2449 affects RIPK4
1 |
KW2449 inhibits RIPK4. 1 / 1
1 |

tas
No evidence text available
KW2449 affects RIPK1
1 |
KW2449 inhibits RIPK1. 1 / 1
1 |

tas
No evidence text available
KW2449 affects RIOK3
1 |
KW2449 inhibits RIOK3. 1 / 1
1 |

tas
No evidence text available
KW2449 affects RIOK1
1 |
KW2449 inhibits RIOK1. 1 / 1
1 |

tas
No evidence text available
KW2449 affects RET
1 |
KW2449 inhibits RET. 1 / 1
1 |

tas
No evidence text available
KW2449 affects PTK2B
1 |
KW2449 inhibits PTK2B. 1 / 1
1 |

tas
No evidence text available
KW2449 affects PRPF4B
1 |
1 |

tas
No evidence text available
KW2449 affects PRKG2
1 |
KW2449 inhibits PRKG2. 1 / 1
1 |

tas
No evidence text available
KW2449 affects PRKD3
1 |
KW2449 inhibits PRKD3. 1 / 1
1 |

tas
No evidence text available
KW2449 affects PRKAA2
1 |
1 |

tas
No evidence text available
KW2449 affects PRKAA1
1 |
1 |

tas
No evidence text available
KW2449 affects PLK4
1 |
KW2449 inhibits PLK4. 1 / 1
1 |

tas
No evidence text available
KW2449 affects PKN2
1 |
KW2449 inhibits PKN2. 1 / 1
1 |

tas
No evidence text available
KW2449 affects PKN1
1 |
KW2449 inhibits PKN1. 1 / 1
1 |

tas
No evidence text available
KW2449 affects PIP5K1A
1 |
1 |

tas
No evidence text available
KW2449 affects PIP4K2B
1 |
1 |

tas
No evidence text available
KW2449 affects PHKG2
1 |
KW2449 inhibits PHKG2. 1 / 1
1 |

tas
No evidence text available
KW2449 affects PHKG1
1 |
KW2449 inhibits PHKG1. 1 / 1
1 |

tas
No evidence text available
KW2449 affects PDPK1
1 |
KW2449 inhibits PDPK1. 1 / 1
1 |

tas
No evidence text available
KW2449 affects PDGFRB
1 |
1 |

tas
No evidence text available
KW2449 affects PDGFRA
1 |
1 |

tas
No evidence text available
KW2449 affects PAK5
1 |
KW2449 inhibits PAK5. 1 / 1
1 |

tas
No evidence text available
KW2449 affects PAK3
1 |
KW2449 inhibits PAK3. 1 / 1
1 |

tas
No evidence text available
KW2449 affects NUAK2
1 |
KW2449 inhibits NUAK2. 1 / 1
1 |

tas
No evidence text available
KW2449 affects NTRK3
1 |
KW2449 inhibits NTRK3. 1 / 1
1 |

tas
No evidence text available
KW2449 affects NTRK2
1 |
KW2449 inhibits NTRK2. 1 / 1
1 |

tas
No evidence text available
KW2449 affects NTRK1
1 |
KW2449 inhibits NTRK1. 1 / 1
1 |

tas
No evidence text available
KW2449 affects NEK9
1 |
KW2449 inhibits NEK9. 1 / 1
1 |

tas
No evidence text available
KW2449 affects NEK7
1 |
KW2449 inhibits NEK7. 1 / 1
1 |

tas
No evidence text available
KW2449 affects NEK6
1 |
KW2449 inhibits NEK6. 1 / 1
1 |

tas
No evidence text available
KW2449 affects MYO3A
1 |
KW2449 inhibits MYO3A. 1 / 1
1 |

tas
No evidence text available
KW2449 affects MYLK4
1 |
KW2449 inhibits MYLK4. 1 / 1
1 |

tas
No evidence text available
KW2449 affects MYLK3
1 |
KW2449 inhibits MYLK3. 1 / 1
1 |

tas
No evidence text available
KW2449 affects MYLK2
1 |
KW2449 inhibits MYLK2. 1 / 1
1 |

tas
No evidence text available
KW2449 affects MYLK
1 |
KW2449 inhibits MYLK. 1 / 1
1 |

tas
No evidence text available
KW2449 affects MUSK
1 |
KW2449 inhibits MUSK. 1 / 1
1 |

tas
No evidence text available
KW2449 affects MST1R
1 |
KW2449 inhibits MST1R. 1 / 1
1 |

tas
No evidence text available
KW2449 affects MINK1
1 |
KW2449 inhibits MINK1. 1 / 1
1 |

tas
No evidence text available
KW2449 affects MET
1 |
KW2449 inhibits MET. 1 / 1
1 |

tas
No evidence text available
KW2449 affects MERTK
1 |
KW2449 inhibits MERTK. 1 / 1
1 |

tas
No evidence text available
KW2449 affects MELK
1 |
KW2449 inhibits MELK. 1 / 1
1 |

tas
No evidence text available
KW2449 affects MARK4
1 |
KW2449 inhibits MARK4. 1 / 1
1 |

tas
No evidence text available
KW2449 affects MARK2
1 |
KW2449 inhibits MARK2. 1 / 1
1 |

tas
No evidence text available
KW2449 affects MARK1
1 |
KW2449 inhibits MARK1. 1 / 1
1 |

tas
No evidence text available
KW2449 affects MAPK9
1 |
KW2449 inhibits MAPK9. 1 / 1
1 |

tas
No evidence text available
KW2449 affects MAPK8
1 |
KW2449 inhibits MAPK8. 1 / 1
1 |

tas
No evidence text available
KW2449 affects MAPK10
1 |
1 |

tas
No evidence text available
KW2449 affects MAP4K5
1 |
1 |

tas
No evidence text available
KW2449 affects MAP4K4
1 |
1 |

tas
No evidence text available
KW2449 affects MAP4K3
1 |
1 |

tas
No evidence text available
KW2449 affects MAP4K2
1 |
1 |

tas
No evidence text available
KW2449 affects MAP4K1
1 |
1 |

tas
No evidence text available
KW2449 affects MAP3K9
1 |
1 |

tas
No evidence text available
KW2449 affects MAP3K7
1 |
1 |

tas
No evidence text available
KW2449 affects MAP3K3
1 |
1 |

tas
No evidence text available
KW2449 affects MAP3K20
1 |
1 |

tas
No evidence text available
KW2449 affects MAP3K2
1 |
1 |

tas
No evidence text available
KW2449 affects MAP3K19
1 |
1 |

tas
No evidence text available
KW2449 affects MAP3K13
1 |
1 |

tas
No evidence text available
KW2449 affects MAP3K12
1 |
1 |

tas
No evidence text available
KW2449 affects MAP2K6
1 |
1 |

tas
No evidence text available
KW2449 affects MAP2K5
1 |
1 |

tas
No evidence text available
KW2449 affects MAP2K4
1 |
1 |

tas
No evidence text available
KW2449 affects MAP2K3
1 |
1 |

tas
No evidence text available
KW2449 affects MAP2K2
1 |
1 |

tas
No evidence text available
KW2449 affects MAP2K1
1 |
1 |

tas
No evidence text available
KW2449 affects LTK
1 |
KW2449 inhibits LTK. 1 / 1
1 |

tas
No evidence text available
KW2449 affects LRRK2
1 |
KW2449 inhibits LRRK2. 1 / 1
1 |

tas
No evidence text available
KW2449 affects KIT
1 |
KW2449 inhibits KIT. 1 / 1
1 |

tas
No evidence text available
KW2449 affects KDR
1 |
KW2449 inhibits KDR. 1 / 1
1 |

tas
No evidence text available
KW2449 affects JAK3
1 |
KW2449 inhibits JAK3. 1 / 1
1 |

tas
No evidence text available
KW2449 affects JAK2
1 |
KW2449 inhibits JAK2. 1 / 1
1 |

tas
No evidence text available
KW2449 affects JAK1
1 |
KW2449 inhibits JAK1. 1 / 1
1 |

tas
No evidence text available
KW2449 affects ITK
1 |
KW2449 inhibits ITK. 1 / 1
1 |

tas
No evidence text available
KW2449 affects IRAK4
1 |
KW2449 inhibits IRAK4. 1 / 1
1 |

tas
No evidence text available
KW2449 affects IRAK3
1 |
KW2449 inhibits IRAK3. 1 / 1
1 |

tas
No evidence text available
KW2449 affects IRAK1
1 |
KW2449 inhibits IRAK1. 1 / 1
1 |

tas
No evidence text available
KW2449 affects INSRR
1 |
KW2449 inhibits INSRR. 1 / 1
1 |

tas
No evidence text available
KW2449 affects INSR
1 |
KW2449 inhibits INSR. 1 / 1
1 |

tas
No evidence text available
KW2449 affects IKBKE
1 |
KW2449 inhibits IKBKE. 1 / 1
1 |

tas
No evidence text available
KW2449 affects IKBKB
1 |
KW2449 inhibits IKBKB. 1 / 1
1 |

tas
No evidence text available
KW2449 affects IGF1R
1 |
KW2449 inhibits IGF1R. 1 / 1
1 |

tas
No evidence text available
KW2449 affects I836L+D
| 1
KW2449 inhibits I836L+D. 1 / 1
| 1

reach
"Sorafenib and KW2449 inhibited growth of all but 5 mutants (D835Y, D835L+ K, I836L+ D, D593D and D835A for sorafenib; D835Y, D835L+ K, I836L+ D, D593D and I836S for KW2449)."
KW2449 affects HUNK
1 |
KW2449 inhibits HUNK. 1 / 1
1 |

tas
No evidence text available
KW2449 affects HIPK3
1 |
KW2449 inhibits HIPK3. 1 / 1
1 |

tas
No evidence text available
KW2449 affects HIPK2
1 |
KW2449 inhibits HIPK2. 1 / 1
1 |

tas
No evidence text available
KW2449 affects HIPK1
1 |
KW2449 inhibits HIPK1. 1 / 1
1 |

tas
No evidence text available
KW2449 affects HDACIs
| 1
HDACIs binds KW2449. 1 / 1
| 1

reach
"Interactions between KW2449 and HDACIs were first examined in Bcr and Abl + human chronic leukemia cells."
KW2449 affects HDACI
| 1
HDACI binds KW2449. 1 / 1
| 1

reach
"Because HDACIs act through multiple mechanisms, the basis for HDACI and KW2449 interactions is likely to be complex."
KW2449 affects GRK4
1 |
KW2449 inhibits GRK4. 1 / 1
1 |

tas
No evidence text available
KW2449 affects GAK
1 |
KW2449 inhibits GAK. 1 / 1
1 |

tas
No evidence text available
KW2449 affects FYN
1 |
KW2449 inhibits FYN. 1 / 1
1 |

tas
No evidence text available
KW2449 affects FLT1
1 |
KW2449 inhibits FLT1. 1 / 1
1 |

tas
No evidence text available
KW2449 affects FGR
1 |
KW2449 inhibits FGR. 1 / 1
1 |

tas
No evidence text available
KW2449 affects FGFR3
1 |
KW2449 inhibits FGFR3. 1 / 1
1 |

tas
No evidence text available
KW2449 affects FGFR2
1 |
KW2449 inhibits FGFR2. 1 / 1
1 |

tas
No evidence text available
KW2449 affects FGFR1
1 |
KW2449 inhibits FGFR1. 1 / 1
1 |

tas
No evidence text available
KW2449 affects FES
1 |
KW2449 inhibits FES. 1 / 1
1 |

tas
No evidence text available
KW2449 affects EPHB6
1 |
KW2449 inhibits EPHB6. 1 / 1
1 |

tas
No evidence text available
KW2449 affects EPHA7
1 |
KW2449 inhibits EPHA7. 1 / 1
1 |

tas
No evidence text available
KW2449 affects EPHA3
1 |
KW2449 inhibits EPHA3. 1 / 1
1 |

tas
No evidence text available
KW2449 affects EPHA1
1 |
KW2449 inhibits EPHA1. 1 / 1
1 |

tas
No evidence text available
KW2449 affects EIF2AK4
1 |
1 |

tas
No evidence text available
KW2449 affects DYRK2
1 |
KW2449 inhibits DYRK2. 1 / 1
1 |

tas
No evidence text available
KW2449 affects DYRK1B
1 |
1 |

tas
No evidence text available
KW2449 affects DYRK1A
1 |
1 |

tas
No evidence text available
KW2449 affects DSTYK
1 |
KW2449 inhibits DSTYK. 1 / 1
1 |

tas
No evidence text available
KW2449 affects DCLK3
1 |
KW2449 inhibits DCLK3. 1 / 1
1 |

tas
No evidence text available
KW2449 affects DAPK3
1 |
KW2449 inhibits DAPK3. 1 / 1
1 |

tas
No evidence text available
KW2449 affects DAPK1
1 |
KW2449 inhibits DAPK1. 1 / 1
1 |

tas
No evidence text available
KW2449 affects D835L+K
| 1
KW2449 inhibits D835L+K. 1 / 1
| 1

reach
"Sorafenib and KW2449 inhibited growth of all but 5 mutants (D835Y, D835L+ K, I836L+ D, D593D and D835A for sorafenib; D835Y, D835L+ K, I836L+ D, D593D and I836S for KW2449)."
KW2449 affects Caspase
| 1
| 1

reach
"HDACIs increase KW2449 mediated caspase activation and inhibition of Bcr and Abl related signaling pathways in IM sensitive and -resistant cells."
KW2449 affects CSNK2A2
1 |
1 |

tas
No evidence text available
KW2449 affects CSNK1G2
1 |
1 |

tas
No evidence text available
KW2449 affects CSNK1E
1 |
1 |

tas
No evidence text available
KW2449 affects CSF1R
1 |
KW2449 inhibits CSF1R. 1 / 1
1 |

tas
No evidence text available
KW2449 affects CLK4
1 |
KW2449 inhibits CLK4. 1 / 1
1 |

tas
No evidence text available
KW2449 affects CLK2
1 |
KW2449 inhibits CLK2. 1 / 1
1 |

tas
No evidence text available
KW2449 affects CLK1
1 |
KW2449 inhibits CLK1. 1 / 1
1 |

tas
No evidence text available
KW2449 affects CIT
1 |
KW2449 inhibits CIT. 1 / 1
1 |

tas
No evidence text available
KW2449 affects CHUK
1 |
KW2449 inhibits CHUK. 1 / 1
1 |

tas
No evidence text available
KW2449 affects CHEK2
1 |
KW2449 inhibits CHEK2. 1 / 1
1 |

tas
No evidence text available
KW2449 affects CHEK1
1 |
KW2449 inhibits CHEK1. 1 / 1
1 |

tas
No evidence text available
KW2449 affects CDK7
1 |
KW2449 inhibits CDK7. 1 / 1
1 |

tas
No evidence text available
KW2449 affects CDK4
1 |
KW2449 inhibits CDK4. 1 / 1
1 |

tas
No evidence text available
KW2449 affects CDK16
1 |
KW2449 inhibits CDK16. 1 / 1
1 |

tas
No evidence text available
KW2449 affects CDK14
1 |
KW2449 inhibits CDK14. 1 / 1
1 |

tas
No evidence text available
KW2449 affects CAMKK2
1 |
1 |

tas
No evidence text available
KW2449 affects CAMKK1
1 |
1 |

tas
No evidence text available
KW2449 affects CAMK1D
1 |
1 |

tas
No evidence text available
1 |

tas
No evidence text available
KW2449 affects C8orf44
1 |
1 |

tas
No evidence text available
KW2449 affects BMPR2
1 |
KW2449 inhibits BMPR2. 1 / 1
1 |

tas
No evidence text available
KW2449 affects BMPR1B
1 |
1 |

tas
No evidence text available
KW2449 affects BMP2K
1 |
KW2449 inhibits BMP2K. 1 / 1
1 |

tas
No evidence text available
KW2449 affects AXL
1 |
KW2449 inhibits AXL. 1 / 1
1 |

tas
No evidence text available
KW2449 affects AURKC
1 |
KW2449 inhibits AURKC. 1 / 1
1 |

tas
No evidence text available
KW2449 affects AURKB
1 |
KW2449 inhibits AURKB. 1 / 1
1 |

tas
No evidence text available
KW2449 affects AURKA
1 |
KW2449 inhibits AURKA. 1 / 1
1 |

tas
No evidence text available
KW2449 affects ANKK1
1 |
KW2449 inhibits ANKK1. 1 / 1
1 |

tas
No evidence text available
KW2449 affects ALK
1 |
KW2449 inhibits ALK. 1 / 1
1 |

tas
No evidence text available
KW2449 affects ACVR2B
1 |
1 |

tas
No evidence text available
KW2449 affects ACVR2A
1 |
1 |

tas
No evidence text available
KW2449 affects ACVR1
1 |
KW2449 inhibits ACVR1. 1 / 1
1 |

tas
No evidence text available
KW2449 affects ABL2
1 |
KW2449 inhibits ABL2. 1 / 1
1 |

tas
No evidence text available
KW2449 affects AAK1
1 |
KW2449 inhibits AAK1. 1 / 1
1 |

tas
No evidence text available
A-674563 affects ceramide
| 1
A-674563 activates ceramide. 1 / 1
| 1

reach
"Further, A-674563 induced pro apoptotic ceramide production in A375cells."
| 1
| 1

reach
"Our results showed that A-674563 dose-dependently inhibited survival and proliferation of U937 AML cells and six lines of human AML progenitor cells, yet sparing human peripheral blood mononuclear leukocytes (PBMCs)."
A-674563 affects cell growth
| 1
A-674563 inhibits cell growth. 1 / 1
| 1

reach
"A-674563, a putative AKT1 inhibitor that also suppresses CDK2 activity, inhibits human NSCLC cell growth more effectively than the pan-AKT inhibitor, MK-2206."
A-674563 affects caspase-3/9
| 1
A-674563 activates caspase-3/9. 1 / 1
| 1

reach
"A-674563 activated caspase-3/9 and apoptosis in the AML cells."
A-674563 affects apoptotic process
| 1
A-674563 activates apoptotic process. 1 / 1
| 1

reach
"A-674563 activated caspase-3/9 and apoptosis in the AML cells."
A-674563 affects TNIK
1 |
1 |

tas
No evidence text available
A-674563 affects TBC1D4
| 1
A-674563 decreases the amount of TBC1D4. 1 / 1
| 1

reach
"However, A-674563 decreases expression of p-MDM2 and p-AS160 in A549 cells and increases expression in the A427 cells."
A-674563 affects STK33
1 |
1 |

tas
No evidence text available
A-674563 affects SPHK1
| 1
A-674563 activates SPHK1. 1 / 1
| 1

reach
"Such an effect on SphK1 signaling by A-674563 appeared independent of Akt blockage."
A-674563 affects SGK2
1 |
1 |

tas
No evidence text available
A-674563 affects RPS6
| 1
A-674563 inhibits RPS6. 1 / 1
| 1

reach
"Further, A-674563 treatment blocked Akt and its downstream S6 Kinase 1 (S6K1) activation in A375 melanoma cells."
A-674563 affects RIOK3
1 |
1 |

tas
No evidence text available
A-674563 affects RIOK1
1 |
1 |

tas
No evidence text available
A-674563 affects PRKCQ
1 |
1 |

tas
No evidence text available
A-674563 affects PRKCH
1 |
1 |

tas
No evidence text available
A-674563 affects PRKCE
1 |
1 |

tas
No evidence text available
A-674563 affects PRKACG
1 |
1 |

tas
No evidence text available
A-674563 affects PKN1
1 |
1 |

tas
No evidence text available
A-674563 affects PKIA
1 |
1 |

drugbank
No evidence text available
A-674563 affects PIP5K1A
1 |
1 |

tas
No evidence text available
A-674563 affects PAK6
1 |
1 |

tas
No evidence text available
A-674563 affects PAK5
1 |
1 |

tas
No evidence text available
A-674563 affects MYLK3
1 |
1 |

tas
No evidence text available
A-674563 affects MYLK
1 |
1 |

tas
No evidence text available
A-674563 affects MDM2
| 1
A-674563 decreases the amount of MDM2. 1 / 1
| 1

reach
"However, A-674563 decreases expression of p-MDM2 and p-AS160 in A549 cells and increases expression in the A427 cells."
A-674563 affects MAPK15
1 |
1 |

tas
No evidence text available
A-674563 affects MAP3K7
1 |
1 |

tas
No evidence text available
A-674563 affects MAP3K19
1 |
1 |

tas
No evidence text available
A-674563 affects LATS2
1 |
1 |

tas
No evidence text available
A-674563 affects HIPK3
1 |
1 |

tas
No evidence text available
A-674563 affects HIPK1
1 |
1 |

tas
No evidence text available
A-674563 affects GAK
1 |
A-674563 inhibits GAK. 1 / 1
1 |

tas
No evidence text available
A-674563 affects DYRK4
1 |
1 |

tas
No evidence text available
A-674563 affects DYRK3
1 |
1 |

tas
No evidence text available
A-674563 affects DYRK2
1 |
1 |

tas
No evidence text available
A-674563 affects DYRK1B
1 |
1 |

tas
No evidence text available
A-674563 affects DYRK1A
1 |
1 |

tas
No evidence text available
A-674563 affects DMPK
1 |
1 |

tas
No evidence text available
A-674563 affects Caspase
| 1
A-674563 activates Caspase. 1 / 1
| 1

reach
"A-674563 induced caspase dependent apoptotic death of human melanoma cells, and its cytotoxicity was inhibited with pre-treatment of caspase inhibitors."
A-674563 affects CSNK1E
1 |
1 |

tas
No evidence text available
A-674563 affects CLK4
1 |
1 |

tas
No evidence text available
A-674563 affects CLK3
1 |
1 |

tas
No evidence text available
A-674563 affects CLK2
1 |
1 |

tas
No evidence text available
A-674563 affects CLK1
1 |
1 |

tas
No evidence text available
A-674563 affects CIT
1 |
A-674563 inhibits CIT. 1 / 1
1 |

tas
No evidence text available
A-674563 affects CILK1
1 |
1 |

tas
No evidence text available
A-674563 affects CDKL5
1 |
1 |

tas
No evidence text available
A-674563 affects CDKL2
1 |
1 |

tas
No evidence text available
A-674563 affects CDK9
1 |
1 |

tas
No evidence text available
A-674563 affects CDK7
1 |
1 |

tas
No evidence text available
A-674563 affects CDK14
1 |
1 |

tas
No evidence text available
A-674563 affects CDK1
1 |
1 |

tas
No evidence text available
A-674563 affects CDC7
1 |
1 |

tas
No evidence text available
A-674563 affects CDC42BPG
1 |
1 |

tas
No evidence text available
A-674563 affects CDC42BPB
1 |
1 |

tas
No evidence text available
A-674563 affects CAMKK2
1 |
1 |

tas
No evidence text available
A-674563 affects CAMKK1
1 |
1 |

tas
No evidence text available
A-674563 affects CAMK4
1 |
1 |

tas
No evidence text available
A-674563 affects CAMK2A
1 |
1 |

tas
No evidence text available
1 |

tas
No evidence text available
A-674563 affects BMP2K
1 |
1 |

tas
No evidence text available
A-674563 affects AAK1
1 |
1 |

tas
No evidence text available